Site Terms of Use
The Website is an Internet property of PureHealth Research (“PureHealth,” “we” or “us”). You agree to the following Website Terms of Use in their entirety, when you: (1) access or use the Website; and/or (2) purchase products or services offered on our Website (“Online Products”). The Privacy Policy (“Privacy Policy”) and any and all other applicable PureHealth Research operating rules, policies, price schedules and other supplemental terms and conditions or documents that may be published from time to time, are expressly incorporated herein by reference (collectively, the “Agreement”). Please review the Agreement carefully. If you do not agree to the terms and conditions contained within the Agreement in its entirety, you are not authorized to use the Website in any manner or form whatsoever.

Definitions
The “PureHealth Sites” shall mean all areas and services offered or available on the interactive online service operated by PureHealth Research and/or its affiliates on the World Wide Web. The PureHealth sites consist of information, services and content provided by PureHealth Research and/or its affiliates and/or third parties.

General
PureHealth shall have the right at any time to change or discontinue any aspect or feature of the PureHealth including, but not limited to, the content, hours of availability, and equipment needed for access or use. Such changes, modifications, additions or deletions shall be effective immediately without further notice thereof. Amendments to the terms and conditions contained herein may be given by means including but not limited to, posting on the PureHealth Sites a revised version of this Agreement or notification by electronic mail. Any use of the PureHealth Sites after such notice shall conclusively be deemed to be acceptance of such changes, modifications, additions or deletions. The user agrees to review the terms and conditions of this Agreement periodically to be aware of such revisions.

Use of the PureHealth Sites.

A. The PureHealth Sites contain copyrighted material; trademarks and other proprietary information including text, software, photos, video, graphics, music and sound, and the entire contents of the PureHealth Sites are copyrighted as a collective work under the United States copyright laws. PureHealth is the owner of the copyright in the entire PureHealth Sites. PureHealth owns a copyright in the selection, coordination, arrangement and enhancement of such content, as well as in the content original to it. Each third party content provider owns the copyright in content original to it. You may not modify, publish, transmit, display, participate in the transfer or sale, create derivative works, or in any way exploit the content of the PureHealth Sites or any portion of it. Except as otherwise expressly permitted under copyright law, you may not copy, redistribute, publish, display or commercially exploit any material from the PureHealth Sites without the express permission of PureHealth and, if applicable, the copyright owner. In the event of any permitted copying, redistribution or publication of material from the PureHealth Sites, no changes in or deletion of author attribution, trademark, legend or copyright notice shall be made. You acknowledge that you do not acquire any ownership rights by downloading or copying copyrighted material.

B. You hereby grant to PureHealth and its respective affiliates worldwide, royalty-free, perpetual, irrevocable, non-exclusive right and license to use, reproduce, modify, adapt, publish, translate, create derivative works from, distribute, perform and display any e-mail, video, graphic, data, or information sent by you to PureHealth (in whole or in part) and/or to incorporate it in other works in any form, media or technology now known or later developed.

C. You shall provide PureHealth with accurate, complete and updated information provided by you at the time of your purchase.

D. The PureHealth Sites contain links to other Web sites, resources and advertisers. PureHealth is not responsible for the availability of these external sites nor does it endorse or is it responsible for the contents, advertising, products or other materials made available on or through such external sites. Under no circumstances shall PureHealth be held responsible or liable, directly or indirectly, for any loss or damage caused or alleged to have been caused to a user in connection with the use of or reliance on any content, goods or services available on such external site. You should direct any concerns to such external site’s administrator or web master.

E. You agree not to take any action to interfere with the function or accessibility of the PureHealth Site or to take any action to restrict the access of others thereto.

F. The foregoing provisions of this Section 3 are for the benefit of PureHealth, its affiliates, third party content providers and licensors, and each shall have the right to assert and enforce such provisions directly on its own behalf or jointly with others.

G. PureHealth has carefully designed the PureHealth Site with the purpose of delivering certain content to users in a particular format and with a particular appearance. No third party shall have the right to utilize the content of the PureHealth Site in any way that interferes with that purpose. In particular, PureHealth prohibits any party from displaying the content on the PureHealth Sites in any format where third party advertising or other materials that PureHealth did not authorize in writing is viewed or viewable together with PureHealth’ proprietary content.

Disclaimer of Warranty; Limitation of Liability.

A. YOU EXPRESSLY AGREE THAT USE OF THE PureHealth SITE IS AT YOUR SOLE RISK. NEITHER PureHealth, ITS AFFILIATES NOR ANY OF THEIR RESPECTIVE EMPLOYEES, AGENTS, THIRD PARTY CONTENT PROVIDERS OR LICENSORS WARRANT THAT THE PureHealth WILL BE UNINTERRUPTED OR ERROR FREE; NOR DO THEY MAKE ANY WARRANTY AS TO THE RESULTS THAT MAY BE OBTAINED FROM USE OF THE PureHealth SITE OR AS TO THE ACCURACY, RELIABILITY OR CONTENT OF ANY INFORMATION, SERVICE OR PRODUCTS PROVIDED THROUGH THE SITES.

B. THE PureHealth SITES ARE PROVIDED ON AN “AS IS”, “AS AVAILABLE” BASIS WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.

C. THE DISCLAIMERS OF LIABILITY CONTAINED IN THIS SECTION APPLY TO ANY DAMAGES OR INJURY CAUSED, DIRECTLY OR INDIRECTLY, BY ANY FAILURE OF PERFORMANCE, ERROR, OMISSION, INTERRUPTION, DELETION, DEFECT, DELAY IN OPERATION OR TRANSMISSION, COMPUTER VIRUS, COMMUNICATION LINE FAILURE, THEFT OR DESTRUCTION OR UNAUTHORIZED ACCESS TO, ALTERATION OF, OR USE OF RECORD, WHETHER FOR BREACH OF CONTRACT, TORTUOUS BEHAVIOR, NEGLIGENCE, OR UNDER ANY OTHER CAUSE OF ACTION. YOU SPECIFICALLY ACKNOWLEDGE THAT PureHealth IS NOT LIABLE FOR THE DEFAMATORY, OFFENSIVE OR ILLEGAL CONDUCT OF OTHER USERS OR THIRD PARTIES AND THAT THE RISK OF INJURY FROM THE FOREGOING RESTS ENTIRELY WITH YOU.

D. IN NO EVENT WILL PureHealth OR ANY PERSON OR ENTITY INVOLVED IN CREATING, PRODUCING OR DISTRIBUTING THE PureHealth SITE BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OF OR INABILITY TO USE THE PureHealth OR OUT OF THE BREACH OF ANY WARRANTY. YOU HEREBY ACKNOWLEDGE THAT THE PROVISIONS OF THIS SECTION 4 SHALL APPLY TO ALL CONTENT ON THE PureHealth SITE. PureHealth’S LIABILITY TO USERS, IF ANY, SHALL IN NO EVENT EXCEED THE TOTAL AMOUNT PAID TO PureHealth.

E. PureHealth NEITHER ENDORSES NOR IS RESPONSIBLE FOR THE ACCURACY OR RELIABILITY OF ANY OPINION, ADVICE OR STATEMENT ON THE PureHealth SITE, NOR FOR ANY OFFENSIVE, DEFAMATORY OR OBSCENE POSTING MADE BY. UNDER NO CIRCUMSTANCES WILL PureHealth BE LIABLE FOR ANY LOSS OR DAMAGE CAUSED BY YOUR RELIANCE ON INFORMATION OBTAINED THROUGH THE CONTENT ON THE PureHealth SITE. IT IS YOUR RESPONSIBILITY TO EVALUATE THE ACCURACY, COMPLETENESS OR USEFULNESS OF ANY INFORMATION, OPINION, ADVICE OR OTHER CONTENT AVAILABLE THROUGH THE PureHealth SITES. PLEASE SEEK THE ADVICE OF PROFESSIONALS, AS APPROPRIATE, REGARDING THE EVALUATION OF ANY SPECIFIC INFORMATION, OPINION, ADVICE OR OTHER CONTENT, INCLUDING BUT NOT LIMITED TO FINANCIAL, HEALTH, OR LIFESTYLE INFORMATION, OPINION, ADVICE OR OTHER CONTENT.

F. PureHealth DOES NOT ENDORSE, WARRANT OR GUARANTEE ANY PRODUCTS OR SERVICES OFFERED THROUGH THE PureHealth SITES (WITH THE SOLE EXCEPTION BEING WRITTEN WARRANTIES PROVIDED IN CONNECTION WITH PureHealth PRODUCTS OR SERVICES) AND WILL NOT BE A PARTY TO OR IN ANY WAY MONITOR ANY TRANSACTION BETWEEN USERS AND THIRD PARTY PROVIDERS OF PRODUCTS OR SERVICES. AS WITH THE PURCHASE OF A PRODUCT OR SERVICE THROUGH ANY MEDIUM OR IN ANY ENVIRONMENT, YOU SHOULD USE YOUR BEST JUDGMENT AND EXERCISE CAUTION WHERE APPROPRIATE. PureHealth MAKES PRODUCTS OR SERVICES AVAILABLE ON THE PureHealth SITES WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.

Indemnification
You agree to defend, indemnify and hold harmless PureHealth, its affiliates and their respective directors, officers, employees and agents from and against all claims and expenses, including attorneys’ fees, arising out of the use by you of the PureHealth Sites, including claims by other users of your equipment, access or membership.

Termination
PureHealth shall have the right to immediately terminate this Agreement with respect to any user which PureHealth, in its sole discretion, considers to be unacceptable, or in the event of any breach by you of this Agreement. The provisions of Sections 3, 4, 5, 6, 7, and 8 shall survive termination of this Agreement.

Trademarks
All trademarks appearing on the PureHealth Sites are the property of their respective owners, including, in some instances, PureHealth, and/or affiliated companies.

Title & Risk of Loss
All Online Products purchased from PureHealth are made pursuant to a shipment contract with our carriers. That means that risk of loss and title for the Online Products purchased pass to you upon our delivery to the carrier.

Miscellaneous
This Agreement and any operating rules for the PureHealth Sites established by PureHealth constitute the entire agreement of the parties with respect to the subject matter hereof, and supersede all previous written or oral agreements between the parties with respect to such subject matter. This Agreement shall be construed in accordance with the laws of the State of Texas without regard to its conflict of laws rules. Any dispute arising under or relating to this Agreement or any PureHealth Site shall be brought in state or federal courts in Austin, Texas, and you hereby irrevocably consent to the jurisdiction of such courts. No waiver by either party of any breach or default hereunder shall be deemed to be a waiver of any preceding or subsequent breach or default. You also give full permission to PureHealth to charge other accounts provided on items purchased and not paid for. The section headings used herein are for convenience only and shall not be given any legal import.

Allure

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This policy was last modified on 12/14/15

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Site Terms of Use
The Website is an Internet property of PureHealth Research (“PureHealth,” “we” or “us”). You agree to the following Website Terms of Use in their entirety, when you: (1) access or use the Website; and/or (2) purchase products or services offered on our Website (“Online Products”). The Privacy Policy (“Privacy Policy”) and any and all other applicable PureHealth Research operating rules, policies, price schedules and other supplemental terms and conditions or documents that may be published from time to time, are expressly incorporated herein by reference (collectively, the “Agreement”). Please review the Agreement carefully. If you do not agree to the terms and conditions contained within the Agreement in its entirety, you are not authorized to use the Website in any manner or form whatsoever.

Definitions
The “PureHealth Sites” shall mean all areas and services offered or available on the interactive online service operated by PureHealth Research and/or its affiliates on the World Wide Web. The PureHealth sites consist of information, services and content provided by PureHealth Research and/or its affiliates and/or third parties.

General
PureHealth shall have the right at any time to change or discontinue any aspect or feature of the PureHealth including, but not limited to, the content, hours of availability, and equipment needed for access or use. Such changes, modifications, additions or deletions shall be effective immediately without further notice thereof. Amendments to the terms and conditions contained herein may be given by means including but not limited to, posting on the PureHealth Sites a revised version of this Agreement or notification by electronic mail. Any use of the PureHealth Sites after such notice shall conclusively be deemed to be acceptance of such changes, modifications, additions or deletions. The user agrees to review the terms and conditions of this Agreement periodically to be aware of such revisions.

Use of the PureHealth Sites.

A. The PureHealth Sites contain copyrighted material; trademarks and other proprietary information including text, software, photos, video, graphics, music and sound, and the entire contents of the PureHealth Sites are copyrighted as a collective work under the United States copyright laws. PureHealth is the owner of the copyright in the entire PureHealth Sites. PureHealth owns a copyright in the selection, coordination, arrangement and enhancement of such content, as well as in the content original to it. Each third party content provider owns the copyright in content original to it. You may not modify, publish, transmit, display, participate in the transfer or sale, create derivative works, or in any way exploit the content of the PureHealth Sites or any portion of it. Except as otherwise expressly permitted under copyright law, you may not copy, redistribute, publish, display or commercially exploit any material from the PureHealth Sites without the express permission of PureHealth and, if applicable, the copyright owner. In the event of any permitted copying, redistribution or publication of material from the PureHealth Sites, no changes in or deletion of author attribution, trademark, legend or copyright notice shall be made. You acknowledge that you do not acquire any ownership rights by downloading or copying copyrighted material.

B. You hereby grant to PureHealth and its respective affiliates worldwide, royalty-free, perpetual, irrevocable, non-exclusive right and license to use, reproduce, modify, adapt, publish, translate, create derivative works from, distribute, perform and display any e-mail, video, graphic, data, or information sent by you to PureHealth (in whole or in part) and/or to incorporate it in other works in any form, media or technology now known or later developed.

C. You shall provide PureHealth with accurate, complete and updated information provided by you at the time of your purchase.

D. The PureHealth Sites contain links to other Web sites, resources and advertisers. PureHealth is not responsible for the availability of these external sites nor does it endorse or is it responsible for the contents, advertising, products or other materials made available on or through such external sites. Under no circumstances shall PureHealth be held responsible or liable, directly or indirectly, for any loss or damage caused or alleged to have been caused to a user in connection with the use of or reliance on any content, goods or services available on such external site. You should direct any concerns to such external site’s administrator or web master.

E. You agree not to take any action to interfere with the function or accessibility of the PureHealth Site or to take any action to restrict the access of others thereto.

F. The foregoing provisions of this Section 3 are for the benefit of PureHealth, its affiliates, third party content providers and licensors, and each shall have the right to assert and enforce such provisions directly on its own behalf or jointly with others.

G. PureHealth has carefully designed the PureHealth Site with the purpose of delivering certain content to users in a particular format and with a particular appearance. No third party shall have the right to utilize the content of the PureHealth Site in any way that interferes with that purpose. In particular, PureHealth prohibits any party from displaying the content on the PureHealth Sites in any format where third party advertising or other materials that PureHealth did not authorize in writing is viewed or viewable together with PureHealth’ proprietary content.

Disclaimer of Warranty; Limitation of Liability.

A. YOU EXPRESSLY AGREE THAT USE OF THE PureHealth SITE IS AT YOUR SOLE RISK. NEITHER PureHealth, ITS AFFILIATES NOR ANY OF THEIR RESPECTIVE EMPLOYEES, AGENTS, THIRD PARTY CONTENT PROVIDERS OR LICENSORS WARRANT THAT THE PureHealth WILL BE UNINTERRUPTED OR ERROR FREE; NOR DO THEY MAKE ANY WARRANTY AS TO THE RESULTS THAT MAY BE OBTAINED FROM USE OF THE PureHealth SITE OR AS TO THE ACCURACY, RELIABILITY OR CONTENT OF ANY INFORMATION, SERVICE OR PRODUCTS PROVIDED THROUGH THE SITES.

B. THE PureHealth SITES ARE PROVIDED ON AN “AS IS”, “AS AVAILABLE” BASIS WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.

C. THE DISCLAIMERS OF LIABILITY CONTAINED IN THIS SECTION APPLY TO ANY DAMAGES OR INJURY CAUSED, DIRECTLY OR INDIRECTLY, BY ANY FAILURE OF PERFORMANCE, ERROR, OMISSION, INTERRUPTION, DELETION, DEFECT, DELAY IN OPERATION OR TRANSMISSION, COMPUTER VIRUS, COMMUNICATION LINE FAILURE, THEFT OR DESTRUCTION OR UNAUTHORIZED ACCESS TO, ALTERATION OF, OR USE OF RECORD, WHETHER FOR BREACH OF CONTRACT, TORTUOUS BEHAVIOR, NEGLIGENCE, OR UNDER ANY OTHER CAUSE OF ACTION. YOU SPECIFICALLY ACKNOWLEDGE THAT PureHealth IS NOT LIABLE FOR THE DEFAMATORY, OFFENSIVE OR ILLEGAL CONDUCT OF OTHER USERS OR THIRD PARTIES AND THAT THE RISK OF INJURY FROM THE FOREGOING RESTS ENTIRELY WITH YOU.

D. IN NO EVENT WILL PureHealth OR ANY PERSON OR ENTITY INVOLVED IN CREATING, PRODUCING OR DISTRIBUTING THE PureHealth SITE BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OF OR INABILITY TO USE THE PureHealth OR OUT OF THE BREACH OF ANY WARRANTY. YOU HEREBY ACKNOWLEDGE THAT THE PROVISIONS OF THIS SECTION 4 SHALL APPLY TO ALL CONTENT ON THE PureHealth SITE. PureHealth’S LIABILITY TO USERS, IF ANY, SHALL IN NO EVENT EXCEED THE TOTAL AMOUNT PAID TO PureHealth.

E. PureHealth NEITHER ENDORSES NOR IS RESPONSIBLE FOR THE ACCURACY OR RELIABILITY OF ANY OPINION, ADVICE OR STATEMENT ON THE PureHealth SITE, NOR FOR ANY OFFENSIVE, DEFAMATORY OR OBSCENE POSTING MADE BY. UNDER NO CIRCUMSTANCES WILL PureHealth BE LIABLE FOR ANY LOSS OR DAMAGE CAUSED BY YOUR RELIANCE ON INFORMATION OBTAINED THROUGH THE CONTENT ON THE PureHealth SITE. IT IS YOUR RESPONSIBILITY TO EVALUATE THE ACCURACY, COMPLETENESS OR USEFULNESS OF ANY INFORMATION, OPINION, ADVICE OR OTHER CONTENT AVAILABLE THROUGH THE PureHealth SITES. PLEASE SEEK THE ADVICE OF PROFESSIONALS, AS APPROPRIATE, REGARDING THE EVALUATION OF ANY SPECIFIC INFORMATION, OPINION, ADVICE OR OTHER CONTENT, INCLUDING BUT NOT LIMITED TO FINANCIAL, HEALTH, OR LIFESTYLE INFORMATION, OPINION, ADVICE OR OTHER CONTENT.

F. PureHealth DOES NOT ENDORSE, WARRANT OR GUARANTEE ANY PRODUCTS OR SERVICES OFFERED THROUGH THE PureHealth SITES (WITH THE SOLE EXCEPTION BEING WRITTEN WARRANTIES PROVIDED IN CONNECTION WITH PureHealth PRODUCTS OR SERVICES) AND WILL NOT BE A PARTY TO OR IN ANY WAY MONITOR ANY TRANSACTION BETWEEN USERS AND THIRD PARTY PROVIDERS OF PRODUCTS OR SERVICES. AS WITH THE PURCHASE OF A PRODUCT OR SERVICE THROUGH ANY MEDIUM OR IN ANY ENVIRONMENT, YOU SHOULD USE YOUR BEST JUDGMENT AND EXERCISE CAUTION WHERE APPROPRIATE. PureHealth MAKES PRODUCTS OR SERVICES AVAILABLE ON THE PureHealth SITES WITHOUT WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO WARRANTIES OF TITLE OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OTHER THAN THOSE WARRANTIES WHICH ARE IMPLIED BY AND INCAPABLE OF EXCLUSION, RESTRICTION OR MODIFICATION UNDER THE LAWS APPLICABLE TO THIS AGREEMENT.

Indemnification
You agree to defend, indemnify and hold harmless PureHealth, its affiliates and their respective directors, officers, employees and agents from and against all claims and expenses, including attorneys’ fees, arising out of the use by you of the PureHealth Sites, including claims by other users of your equipment, access or membership.

Termination
PureHealth shall have the right to immediately terminate this Agreement with respect to any user which PureHealth, in its sole discretion, considers to be unacceptable, or in the event of any breach by you of this Agreement. The provisions of Sections 3, 4, 5, 6, 7, and 8 shall survive termination of this Agreement.

Trademarks
All trademarks appearing on the PureHealth Sites are the property of their respective owners, including, in some instances, PureHealth, and/or affiliated companies.

Title & Risk of Loss
All Online Products purchased from PureHealth are made pursuant to a shipment contract with our carriers. That means that risk of loss and title for the Online Products purchased pass to you upon our delivery to the carrier.

Miscellaneous
This Agreement and any operating rules for the PureHealth Sites established by PureHealth constitute the entire agreement of the parties with respect to the subject matter hereof, and supersede all previous written or oral agreements between the parties with respect to such subject matter. This Agreement shall be construed in accordance with the laws of the State of Texas without regard to its conflict of laws rules. Any dispute arising under or relating to this Agreement or any PureHealth Site shall be brought in state or federal courts in Austin, Texas, and you hereby irrevocably consent to the jurisdiction of such courts. No waiver by either party of any breach or default hereunder shall be deemed to be a waiver of any preceding or subsequent breach or default. You also give full permission to PureHealth to charge other accounts provided on items purchased and not paid for. The section headings used herein are for convenience only and shall not be given any legal import.

PureHealth Research wants you to be completely satisfied with your experience so we have made returning or exchanging products easy. You are backed by a 1-Year Money Back Guarantee and a 1-Year Exchange Guarantee.

Simply return the empty and unused portion of your PureHealth Research product order within 1 year of your billing date for a full refund of the product price.

Return and Exchange Procedures:

Refunds/Exchanges: Contact our customer support center 24 hours a day at Support [at] PureHealthResearch .com, or call us at (888) 558-9836, M – F 9AM – 5PM EST, for a Return Merchandise Authorization Number (RMA#) or an Exchange Merchandise Number (EMA#) and the Return Address.

Return the empty and unused portion of your product, the original invoice and your RMA# or EMA# to ensure proper handling. If you would like to exchange your return for another quality product of equal or lesser value, please indicate what product(s) in your return.

Exchanges: We offer a 1-year exchange program where you can return a product and request that we send you another quality PureHealthResearch product of equal or lesser value with free shipping. All exchanges are final.

Important: Return postage is the responsibility of the customer and we recommend using delivery confirmation to avoid any delays. All packages returned refused or undeliverable will be refunded the cost of the product minus the shipping fees incurred by refusal of the package.

Returns must be received in our offices within 1 year from billing date. All charges (excluding shipping and handling fees) are fully refundable 1 year from the billing date. Exchange requests must be received by our offices within 1 year from the billing date.

Used/Empty product containers may only be returned if adequate time has elapsed to consume the product as directed on the label. For example, we will not accept a six-month supply of empty product containers after only one or two months.

All refunds will be processed within 72 hours of receiving the package. After a return has been processed, it may take up to 5 business days for the Bank to process the refund to the credit card.

PUREHEALTH RESEARCH ALLURE LIFTING FIRMING CREAMCLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Purified Water

Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process
Abstract
Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 °C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.Source:
M. Kawai,N. Yamaguchi andM. Nasu.Journal of Applied Microbiology. Volume 86, Issue 3, pages 496–504, March 1999. DOI: 10.1046/j.1365-2672.1999.00689.xhttp://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.1999.00689.x/full

Isopropyl myristate is used in cosmetic and topical medicinal preparations where good absorption through the skin is desired.

Enhanced transdermal delivery of estradiol in vitro using binary vehicles of isopropyl myristate and short-chain alkanols

Abstract
The effect of binary vehicles of isopropyl myristate (IPM) and short-chain alkanols on the enhancement of skin permeation of estradiol (E2) was studied in vitro using human epidermal membrane. The steady-state fluxes of E2 and solvents across the skin were determined from saturated solutions of neat and binary solvents of IPM and ethanol (EtOH), n-propanol (n-PrOH), n-octanol (n-OcOH), or isopropanol (i-PrOH). While the neat solvents modestly increased the E2 flux, addition of IPM to the alkanols resulted in a synergistic enhancement of the E2 flux. Among the (1:1) binary cosolvents evaluated, i-PrOH produced the highest E2 flux (1.1 μg/cm2 per h), which was 35-fold greater than from water and over 15-fold greater than from the neat solvents. This combination was also the best in terms of relative compositions of the IPM/i-PrOH cosolvents. A strong correlation between E2 and i-PrOH fluxes suggested the enhancement for both permeants. While i-PrOH traversed the skin, IPM was retained in the stratum corneum. The uptake of both IPM and E2 in the stratum corneum was largely increased by adding i-PrOH (up to 50%) to IPM.Source:
Melinda Goldberg-Cettina,Puchun Liu, James Nightingale, Tamie Kurihara-Bergstrom.International Journal of Pharmaceutics.Volume 114, Issue 2, 14 February 1995, Pages 237–245. doi:10.1016/0378-5173(94)00253-2http://www.sciencedirect.com/science/article/pii/0378517394002532

Investigations into the formation and characterization of phospholipid microemulsions. I. Pseudo-ternary phase diagrams of systems containing water-lecithin-alcohol-isopropyl myristate
Abstract
Pseudo-ternary phase diagrams have been constructed for systems comprising of water-lecithin-alcohol-isopropyl myristate. Two types of lecithin were used in this study, namely soybean (Epikuron 200) and egg lecithin (Ovothin 200). Seven short chain alcohols (i.e., n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, tert-butanol and n-pentanol) were investigated as cosurfactants. In each system studied, a large monophasic, isotropic, non-birefringent area was seen to occur along the surfactant/oil axis; while at low oil concentrations, a second isotropic, non-birefringent area, usually associated with a liquid crystalline phase, was observed in many systems. Both isotropic regions were stable at room temperature at least for 3 months. Although no significant difference was observed between the phase diagrams produced by the two types of lecithin, the extent of the isotropic regions was dependent upon both the nature of the cosurfactant and lecithin/cosurfactant mixing ratio (Km).Source:
R. Aboofazeli, M.J. Lawrence. International Journal of Pharmaceutics. Volume 93, Issues 1–3, 31 May 1993, Pages 161–175.doi:10.1016/0378-5173(93)90174-E.http://www.sciencedirect.com/science/article/pii/037851739390174E

Investigations into the formation and characterization of phospholipid microemulsions. III. Pseudo-ternary phase diagrams of systems containing water-lecithin-isopropyl myristate and either an alkanoic acid, amine, alkanediol, polyethylene glycol alkyl ether or alcohol as cosurfactant
Abstract
The phase behaviour of quaternary systems composed of lecithin/isopropyl myristate/water/cosurfactant, at a lecithin: cosurfactant mixing ratio (Km) of 1:1 (on a weight basis) have been investigated by the construction of phase diagrams. The lecithin used in this study was the commercially available soybean lecithin, Epikuron 200 (purity greater than 94% phosphatidylcholine) and the cosurfactants examined were either short (alkyl chain length 4–6) straight-chain alkanoic acids, amines, alkanediols, diethylene glycol alkyl ethers or acohols. With the exception of the amines which appeared to react with lecithin, all the systems showed the area of existence of a stable isotropic region along the surfactant/oil axis (i.e., reverse microemulsion area; L2). In no case was a second isotropic region (i.e., normal microemulsion area; L1) observed, although in certain systems a single clear isotropic region covered virtually the whole of the phase diagram and may have included an L1 region. A liquid crystalline (LC) region was observed only in systems containing either an alkanediol or polyethylene glycol alkyl ether as cosurfactant. It was concluded that the area of existence of the various phase regions was very dependent upon the nature of the cosurfactant used.Source:
R. Aboofazeli, C.B. Lawrence, S.R. Wicks, M.J. Lawrence . International Journal of Pharmaceutics Volume 111, Issue 1, 6 October 1994, Pages 63–72. doi:10.1016/0378-5173(94)90402-2http://www.sciencedirect.com/science/article/pii/0378517394904022

Development of model membranes for percutaneous absorption measurements. I. Isopropyl myristate
Abstract
Studies have been conducted to test the validity of an in vitro model for percutaneous absorption in humans. The system consists of an artificial lipid membrane, which mimics the epidermal barrier, supported in a rotating diffusion cell. The artificial membrane was formed with isopropyl myristate (IPM), a lipid chosen to be representative of those in the stratum corneum. The membrane resistance to penetration has been studied for a range of compounds with diverse physicochemical properties. A positive correlation between transport resistance and the IPM-aqueous partition coefficient is demonstrated. The penetration data obtained from the artificial system are compared with those measured using excised human cadaver skin as the membrane in glass diffusion cells. A reasonable correlation was found between the resistances to diffusion provided by the IPM membrane and by excised skin, although the magnitude of the former was 1000-fold lower than of the latter. However, the IPM membrane did not predict the relatively low resistance of excised human skin to isoquinoline and nicotine. It is suggested that although the artificial membrane described provides a reasonable model for percutaneous absorption, modifications should be made to improve the predictability of the system.Source:
Jonathan Hadgraft, Geoffrey Ridout∗. International Journal of Pharmaceutics. Volume 39, Issues 1–2, September 1987, Pages 149–156. doi:10.1016/0378-5173(87)90210-9.http://www.sciencedirect.com/science/article/pii/0378517387902109

Effect of the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions on barrier properties of mice skin for transdermal permeation of tetracaine hydrochloride: In vitro
Abstract
Effect of composition of lecithin water-in-oil and oil-in-water microemulsion on in vitro transdermal permeation of tetracaine hydrochloride was studied on mice model. The results were compared with an aqueous solution of tetracaine hydrochloride (2.7 mg/ml). In vitro skin flux and permeability coefficients were obtained using the Franz diffusion cell. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) were used to study the mechanism of action of the microemulsion. Micrographs of TEM and CLSM studies were analyzed by using Image Pro Plus image software. Skin flux of tetracaine hydrochloride was found to be dependent on the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions. At lower Km ratio (i.e. 0.5:1 and 0.8:1) of microemulsion, the rate of permeation of tetracaine hydrochloride was higher when compared to the microemulsion of higher Km ratio (1:1 and 1.5:1). Image analysis of TEM micrograph, 6 h after application of lecithin microemulsion, showed 3.5 ± 0.75-fold (p < 0.001) increase in the intercellular space in the epidermis and 3.8 ± 0.4-fold (p < 0.001) enhancement in upper dermis. CLMS results show that sweat gland and hair follicles also provided path for permeation of the drug through the skin.Source:
Mohammad Changez ,Manoj Varshney, Jadish Chander, Amit Kumar Dinda. Colloids and Surfaces B: Biointerfaces. Volume 50, Issue 1, 1 June 2006, Pages 18–25. doi:10.1016/j.colsurfb.2006.03.018http://europepmc.org/abstract/MED/16690263

Structural characterisation of water–Tween 40®/Imwitor 308®–isopropyl myristate microemulsions using different experimental methods
Abstract
Pharmaceutically usable microemulsion systems were prepared from water and isopropyl myristate with a constant amount of Tween 40® and Imwitor 308® at a mass ratio of 1. Their type and structure were examined by measuring density and surface tension, and by viscometry, electric conductivity, differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS), and the degree of agreement between the techniques was assessed. A model based on monodisperse hard spheres adequately fits the SAXS data in W/O microemulsions predicting, depending on composition, elongated or spherical droplets. It also suggests the involvement of strong attractive interactions in O/W systems. Results of conductivity, viscosity, density and surface tension measurements confirm the prediction of a percolation transition to a bicontinuous structure. DSC detects the degree of water interaction with surfactants thus identifying the type of microemulsion. The conclusions from all the techniques agree well and indicate that such studies could also be carried out on more complex systems. In future, the ability to determine type and structure of such microemulsion systems could enable partitioning and release rates of drugs from microemulsions to be predicted.Source:
F Podlogar, M Gašperlin, M Tomšič, A Jamnik, M.Bešter Rogač. International Journal of Pharmaceutics. Volume 276, Issues 1–2, 19 May 2004, Pages 115–128. doi:10.1016/j.ijpharm.2004.02.018http://www.sciencedirect.com/science/article/pii/S0378517304001334

Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels
Abstract
The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) through a synthetic membrane and abdominal rat skin from carbopol gels was investigated using Franz-type diffusion cells. The combined effect of isopropyl myristate (IPM) and PG was also evaluated. It was found that the penetration through the synthetic membrane was well described by the Higuchi model. The gel containing 40% PG showed the highest release rate, indicating that a releasing maximum exists for PG content which provides the fully solubilized drug in the vehicle. When using rat skin as the barrier, the penetration rate was controlled by the membrane. DFS flux decreased with increasing PG content of the gels due to an increase of the drug affinity to the vehicle. A cosolvent action of PG was evident. However, the combination of PG and IPM resulted in a synergistic enhancement of DFS flux. Maximum enhancing activity was obtained from gels containing 40% PG, which yielded an enhancement ratio of about 8. Increasing IPM content from 3 to 5% increased the flux and decreased the lag time taken to reach a steady-state level.Source:
A. Arellano, S. Santoyo, C. Martı́n, P. Ygartua. European Journal of Pharmaceutical Sciences. Volume 7, Issue 2, 1 January 1999, Pages 129–135. doi:10.1016/S0928-0987(98)00010-4http://www.sciencedirect.com/science/article/pii/S0928098798000104

Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo
Abstract
Purpose: The objective of this study was to determine the availability of the topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following its administration in formulations containing isopropyl myristate and ethanol. Methods: The ventral forearms of human volunteers were treated for 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl myristate (IPM), in ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period, the treated sites were carefully cleaned of excess vehicle and the SC was progressively removed by sequential tape stripping. TBF was quantified in the SC by: (a) extraction of the tape strips and subsequent HPLC analysis; and (b) attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each sequentially exposed SC surface during the tape stripping procedure. Results: The concentration profile of TBF in the SC (i.e. drug concentration as a function of depth in the membrane) was fitted to the appropriate solution of Fick’s second law of diffusion, allowing thereby the drug’s SC/vehicle partition coefficient (K) and characteristic diffusion parameter (D/L2, where D is the diffusivity of TBF in the SC of thickness L) to be deduced.Conclusions: While D/L2 for TBF derived from the three vehicles remained essentially constant, the drug’s partitioning into the SC was significantly higher from formulations containing ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC results supported these deductions.Source:
Ingo Alberti, Yogeshvar N Kalia, Aarti Naik, Jean-Daniel Bonny, Richard H Guy. International Journal of Pharmaceutics. Volume 219, Issues 1–2, 21 May 2001, Pages 11–19. doi:10.1016/S0378-5173(01)00616-0.http://www.sciencedirect.com/science/article/pii/S0378517301006160

Interfacial Composition and Thermodynamics of Formation of Water/Isopropyl Myristate Water-in-Oil Microemulsions Stabilized by Butan-1-ol and Surfactants Like Cetyl Pyridinium Chloride, Cetyl Trimethyl Ammonium Bromide, and Sodium Dodecyl Sulfate
The stabilization and destabilization of water-in-oil (w/o) microemulsion under varied amounts of surfactant and water and varied temperature by mixing with butan-1-ol and isopropyl myristate have been studied in detail. The surfactants used were sodium dodecyl sulfate, cetyl trimethyl ammonium bromide, and cetyl pyridinium chloride. The distribution of cosurfactant (butan-1-ol) between the interface and the oil at the threshold level of stability has been examined, and the thermodynamics of the transfer process of the cosurfactant from the oil to the interface have been evaluated. The structural parameters (dimension, population density, and water pool radius) of the dispersed water droplets in the oil phase have been also evaluated along with the examination of the interfacial population of surfactant and cosurfactant. A rational analysis of the results has been attempted.Source:
S. K. Hait and S. P. Moulik. Centre for Surface Science, Department of Chemistry, Jadavpur University, Calcutta 700 032, India. Langmuir, 2002, 18 (18), pp 6736–6744
DOI: 10.1021/la011504thttp://pubs.acs.org/doi/abs/10.1021/la011504t

Stearyl Alcohol

Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol help to form emulsions and prevent an emulsion from separating into its oil and liquid components. These ingredients also reduce the tendency of finished products to generate foam when shaken. When used in the formulation of skin care products, Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol act as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.

Effect of cetostearyl alcohol on stabilization of oil-in-water emulsion: I. Difference in the effect by mixing cetyl alcohol with stearyl alcohol
Abstract
It is known that an oil-in-water emulsion increases in consistency and stability on addition of cetostearyl alcohol. When either cetyl alcohol or stearyl alcohol was added individually, the emulsion stability decreased. On storage at room temperature, unstable emulsions decreased in consistency and many particles (not visible immediately after preparation) appeared. The particles were determined to be crystals of the alcohol added. When both alcohols were included in the formulation simultaneously in the appropriate ratio, the emulsions were stable and did not show such changes. This difference in stability can be explained in relation to polymorphism of the alcohols.Source:
S Fukushima,M Takahashi,M Yamaguchi. Journal of Colloid and Interface Science
Volume 57, Issue 2, November 1976, Pages 201-206. doi:10.1016/0021-9797(76)90193-4http://www.sciencedirect.com/science/article/pii/0021979776901934

Contact Dermatitis From Stearyl Alcohol and Propylene Glycol in Fluocinonide Cream
Abstract
A young woman being treated for linear scleroderma became allergic to fluocinonide (Lidex) cream while using it with occlusion. She was able to continue treatment with fluocinonide ointment without an adverse reaction.
Patch testing with the ingredients of the cream demonstrated sensitization to an impurity in commercial stearyl alcohol and irritation from propylene glycol. The woman had no adverse reactions to fluocinonide ointment because this preparation contains no stearyl alcohol and very little propylene glycol.
This case reemphasizes the important role of vehicles in contact allergy and indicates that allergic sensitization may be induced despite the presence of a potent topical steroid.Source:
Ronald N. Shore, MD; Walter B. Shelley, MD, PhD. Arch Dermatol. 1974;109(3):397-399. doi:10.1001/archderm.1974.01630030055015.http://archderm.jamanetwork.com/article.aspx?articleid=533859

Tempering influence on oxygen and water vapor transmission through a stearyl alcohol film
Abstract
Stearyl alcohol was layered on a filter paper support and tested for resistance to O2 and water vapor transmission following tempering. Tempering at 48C for 14 or 35 days caused the resistance to O2and water vapor transmission to increase. The resistance to O2 and water vapor transport was increased 80% and 50% respectively, after 35 days. Likely mechanistic explanations include the healing of crystal imperfections and the development of a more extensive and better linked arrangement of lipid crystalline platelets.Source:
J. J. Kester, O. Fennema. Journal of the American Oil Chemists’ Society. August 1989, Volume 66, Issue 8, pp 1154-1157.http://link.springer.com/article/10.1007/BF02670102

Phase diagram of mixtures of stearic acid and stearyl alcohol
Abstract
Stearyl alcohol (98.4%), stearic acid (96.0%) and their binary mixtures were investigated by differential scanning calorimetry (DSC) at a heating and cooling rate of 10 K min−1. The phase diagrams on heating and cooling were constructed and showed a eutectic behavior for the solid–liquid equilibrium line. In the heating phase diagram, the eutectic line was not always visible due to the existence of a phase transition in the solid state. A shift in the eutectic phase composition towards the acid was observed on cooling. The cooling and heating phase diagrams further differed in the fact that only two exotherms were observed during cooling where three endotherms were observed during heating. A plot of the enthalpy of the mixtures versus the mole fraction shows that different processes are involved in the solid state.Source:
François G Gandolfo, Arjen Bot, Eckhard Flöter. Thermochimica Acta. Volume 404, Issues 1–2, 4 September 2003, Pages 9–17. doi:10.1016/S0040-6031(03)00086-8http://www.sciencedirect.com/science/article/pii/S0040603103000868

Glyceryl Stearate

Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis
Background/aims: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin.
Conclusions: Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis.Source:
M. Lodén,A.-C. Andersson,C. Andersson,T. Frödin, H. Öman and M. Lindberg. Skin Research and Technology. Volume 7, Issue 4, pages 209–213, November 2001. DOI: 10.1034/j.1600-0846.2001.70401.xhttp://onlinelibrary.wiley.com/doi/10.1034/j.1600-0846.2001.70401.x/abstract

PEG-100 Stearate

PEG-100 Stearate is made by combining natural oils (oftentimes palm or coconut) with Stearic Acid to form a water-soluble ester. It can also be a synthetic polymer made by combining Oxirane (Ethylene Oxide) and fatty acids (source). PEG-100 Stearate is primarily used by the cosmetics and beauty care industry as an emollient, an emulsifier and a moisturizer, although PEG Stearates in general are also known to clean the skin and hair by helping water to mix with oil and dirt so that they can be rinsed away, according to CosmeticsInfo.org.

Unexpected skin barrier influence from nonionic emulsifiers
Abstract
Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.Source:
Ebba Bárány, Magnus Lindberg, Marie Lodén. International Journal of Pharmaceutics. Volume 195, Issues 1–2, 15 February 2000, Pages 189–195. doi:10.1016/S0378-5173(99)00388-9http://www.sciencedirect.com/science/article/pii/S0378517399003889

Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions
Abstract
Multiple W/O/W emulsions for topical application using Span 80 as a lipophilic emulsifier were prepared. Several hydrophilic emulsifiers were tested in respect of their suitability for the preparation of multiple emulsions. In addition, the effect of different oil-phase compositions on emulsion stability was investigated. The physicochemical parameters of the formulations were characterized and their long-term stability was evaluated by means of rheological measurements, droplet size observations and conductivity analysis.
As discovered, the modification of an oil-phase composition results in a decrease in the diffusion coefficient of water and water-soluble substances and, consequently, in enhanced stability. The influence of the release of electrolytes from the inner to the outer water phase on the emulsion stability behaviour was investigated. It was found, that the effect of the hydrophilic emulsifiers on the formulation properties is related not only to its HLB value, but rather to its chemical composition.
As a result, polyethoxylated ethers of fatty alcohols (C = 16–18) with HLBs between 15.3 and 16.2 appear to be the most suitable ones for creating stable formulations.Source:
T. Schmidts, , D. Dobler, C. Nissing, F. Runkel. Journal of Colloid and Interface Science. Volume 338, Issue 1, 1 October 2009, Pages 184–192. doi:10.1016/j.jcis.2009.06.033doi:10.1016/j.jcis.2009.06.033http://www.sciencedirect.com/science/article/pii/S0021979709007632

Exposure data for cosmetic products: lipstick, body lotion, and face cream
Abstract
Accurate exposure information for cosmetic products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of cosmetic product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. The study included three widely used cosmetic product types: lipstick, body lotion, and face cream. Three hundred and sixty women, ages 19–65 years, who regularly use the products of interest, were recruited at ten different geographical locations within the US. The number of recruits was chosen to ensure a minimum of 300 completes per product type. Subjects were provided with prototype test products, and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analysis of the data was conducted to derive summary distribution of use patterns. The mean and median usage per application, respectively, for the three products was: face cream, 1.22 g and 0.84 g; lipstick, 10 mg and 5 mg; and body lotion, 4.42 g and 3.45 g. The mean and median usage per day for the three products was: face cream, 2.05 g and 1.53 g; lipstick, 24 mg and 13 mg; and body lotion, 8.70 g and 7.63 g. The mean number of applications per day for face cream and lipstick was 1.77 and 2.35, respectively. For body lotion, the mean number of applications per day was dependent on body area, and was 2.12, 1.52, 1.11, 0.95, 0.43, 0.26, and 0.40 for hands, arms, legs, feet, neck and throat, back, and other body areas, respectively. The effect of product preference on use practices was also investigated. This study provides current cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.Source:
L.J. Loretz, A.M. Api, L.M. Barraj, J. Burdick, W.E. Dressler, S.D. Gettings, H. Han Hsu, Y.H.L. Pan, T.A. Re, K.J. Renskers, A. Rothenstein, C.G. Scrafford, C. Sewall. Food and Chemical Toxicology. Volume 43, Issue 2, February 2005, Pages 279–291. doi:10.1016/j.fct.2004.09.016http://www.sciencedirect.com/science/article/pii/S0278691504003138 /

Selective hydrogenolysis of glycerol to propylene glycol on Cu–ZnO catalysts
Abstract
Hydrogenolysis of biomass-derived glycerol is an alternative route to sustainable production of propylene glycol. Cu–ZnO catalysts were prepared by coprecipitation with a range of Cu/Zn atomic ratio (0.6–2.0) and examined in glycerol hydrogenolysis to propylene glycol at 453–513 K and 4.2 MPa H2. These catalysts possess acid and hydrogenation sites required for bifunctional glycerol reaction pathways, most likely involving glycerol dehydration to acetol and glycidol intermediates on acidic ZnO surfaces, and their subsequent hydrogenation on Cu surfaces. Glycerol hydrogenolysis conversions and selectivities depend on Cu and ZnO particle sizes. Smaller ZnO and Cu domains led to higher conversions and propylene glycol selectivities, respectively. A high propylene glycol selectivity (83.6%), with a 94.3% combined selectivity to propylene glycol and ethylene glycol (also a valuable product) was achieved at 22.5% glycerol conversion at 473 K on Cu–ZnO (Cu/Zn = 1.0) with relatively small Cu particles. Reaction temperature effects showed that optimal temperatures (e.g. 493 K) are required for high propylene glycol selectivities, probably as a result of optimized adsorption and transformation of the reaction intermediates on the catalyst surfaces. These preliminary results provide guidance for the synthesis of more efficient Cu–ZnO catalysts and for the optimization of reaction parameters for selective glycerol hydrogenolysis to produce propylene glycol.Source:
Shuai Wang, Haichao Liu. Catalysis Letters. August 2007, Volume 117, Issue 1-2, pp 62-67.http://link.springer.com/article/10.1007/s10562-007-9106-9

Low-pressure hydrogenolysis of glycerol to propylene glycol
Abstract
Hydrogenolysis of glycerol to propylene glycol was performed using nickel, palladium, platinum, copper, and copper-chromite catalysts. The effects of temperature, hydrogen pressure, initial water content, choice of catalyst, catalyst reduction temperature, and the amount of catalyst were evaluated. At temperatures above 200 °C and hydrogen pressure of 200 psi, the selectivity to propylene glycol decreased due to excessive hydrogenolysis of the propylene glycol. At 200 psi and 200 °C the pressures and temperaures were significantly lower than those reported in the literature while maintaining high selectivities and good conversions. The yield of propylene glycol increased with decreasing water content. A new reaction pathway for converting glycerol to propylene glycol via an intermediate was validated by isolating the acetol intermediate.Source:
Mohanprasad A. Dasari,Pim-Pahn Kiatsimkul,Willam R. Sutterlin, Galen J. Suppes. Applied Catalysis A: General
Volume 281, Issues 1–2, 18 March 2005, Pages 225–231. doi:10.1016/j.apcata.2004.11.033http://www.sciencedirect.com/science/article/pii/S0926860X0400941X

Hydrolyzed Collagen

Hyrdrolyzed Collagen is a processed form of Collagen that is obtained by breaking down Collagen fibers utilizing heat or caustic solutions. It contains 20 different amino acids, including 8 of the 9 essential amino acids. Essential amino acids cannot be created the human body, which means that the only way our bodies can acquire them is through ingestion.Source:http://www.essen-nutrition.com/blog/entry/hydrolyzed-collagen-health-benefits

Contact Dermatitis to Botanical Extracts.
Abstract
A review of the literature of reported cases of contact dermatitis to a variety of natural herbal extracts is presented. Natural extracts are commonly used ingredients in many cosmetic preparations and homeopathic remedies. Although the term natural botanical extracts inherently purports to have beneficial and benign properties, these extracts can cause adverse reactions in individuals. As such, dermatologists should be cognizant of these agents as possible sources of allergenicity in patients presenting with contact dermatitis.Source:
Kiken, David A.; Cohen, David E. American Journal of Contact Dermatitis:Official Journal of The American Contact Dermatitis Society:September 2002http://journals.lww.com/dermatitis/Abstract/2002/09000/Contact_Dermatitis_to_Botanical_Extracts.10.aspx

Conversion of α-amyrin into centellosides by plant cell cultures of Centella asiatica
Abstract
Plant cell cultures of Centella asiatica produce small quantities of centellosides: madecassosid > asiaticosid > madecassic acid > asiatic acid. To obtain a more efficient production system of these bioactive triterpenoid compounds, we developed a process where the substrate, α-amyrin, was converted into centellosides by cell suspensions of C. asiatica. When α-amyrin in acetone was added at 0.01 mg/ml−1 to the culture medium, together with the permeabilizing agent DMSO, after 7 days nearly 50% had penetrated the plant cells, of which almost 84% was transformed into centellosides. The system therefore efficiently converts α-amyrin into centellosides, thus opening a new possibility for the production of these compounds.Source:
Liliana Hernandez-Vazquez, Mercedes Bonfill, Elisabeth Moyano, Rosa M. Cusido, Arturo Navarro-Ocaña, Javier Palazon. Biotechnology Letters. February 2010, Volume 32, Issue 2, pp 315-319.http://link.springer.com/article/10.1007/s10529-009-0143-x

Capsicum

Green synthesis of silver nanoparticles using Capsicum annuum L. extract
Abstract
Silver nanoparticles (NPs) were rapidly synthesized by treating silver ions with a Capsicum annuum L. extract. The reaction process was simple and convenient to handle, and was monitored using ultraviolet-visible spectroscopy (UV-vis). The effect of Capsicum annuum L.proteins on the formation of silver NPs was investigated using X-ray photoemission spectroscopy (XPS), electrochemical measurements, Fourier-transform infrared spectroscopy(FTIR) and differential spectrum techniques. The morphology and crystalline phase of the NPs were determined from transmission electron microscopy (TEM), selected area electron diffraction (SAED) and X-ray diffraction (XRD) spectra. The results indicated that the proteins, which have amine groups, played a reducing and controlling role during the formation of silver NPs in the solutions, and that the secondary structure of the proteins changed after reaction withsilver ions. The crystalline phase of the NPs changed from polycrystalline to single crystalline and increased in size with increasing reaction time. A recognition–reduction–limited nucleation and growth model was suggested to explain the possible formation mechanism of silver NPs inCapsicum annuum L. extract.Source:Shikuo Li,Yuhua Shen,Anjian Xie,Xuerong Yu,Lingguang Qiu,Li Zhang and Qingfeng Zhang.. Green Chem., 2007,9, 852-858. DOI: 10.1039/B615357Ghttp://pubs.rsc.org/en/content/articlelanding/2007/gc/b615357g#!divAbstract

Changes in Phytochemical and Antioxidant Activity of Selected Pepper Cultivars (Capsicum Species) As Influenced by Maturity
The effect of fruit maturation on changes in carotenoids, flavonoids, total soluble reducing equivalents, phenolic acids, ascorbic acid, and antioxidant activity (AOX) in different pepper types (Capsicum annuum, Capsicum frutescens, and Capsicum chinese) was determined. Generally, the concentration of these chemical constituents increased as the peppers reached maturity. Peppers contained high levels of l-ascorbic acid and carotenoids at maturity, contributing 124−338% of the RDA for vitamin C and 0.33−336 RE/100 g of provitamin A activity, respectively. Levels of phenolic acids, capxanthin, and zeaxanthin generally increased during maturation, whereas the level of lutein declined. Flavonoid concentrations varied greatly among the pepper types analyzed and were negatively correlated to AOX under the conditions of the β-carotene−linoleic assay. Model systems were used to aid in understanding the relationship between flavonoids and AOX. Significant increases in AOX were observed in pepper juice models in response to increasing dilution factors and the presence of EDTA, indicating a pro-oxidant effect due to metal ions in the system. In vitro models demonstrated that increasing levels of flavonoids in combination with constant levels of caffeic and ascorbic acid gave a resultant AOX that was either additive of the two compounds or competitive in their ability to scavenge peroxyl radicals. The model systems were in good agreement with the chemical composition of the pepper cultivars and reflected the interactions affecting AOX. More research is needed to understand the complex interactions that occur among various antioxidants present in pepper extracts.Source:
L. R. Howard , S. T. Talcott , C. H. Brenes , and B. Villalon . J. Agric. Food Chem., 2000, 48 (5), pp 1713–1720. DOI: 10.1021/jf990916thttp://pubs.acs.org/doi/abs/10.1021/jf990916t

The antimicrobial properties of chile peppers (Capsicumspecies) and their uses in Mayan medicine
Abstract
A survey of the Mayan pharmacopoeia revealed that tissues of Capsicum species (Solanaceae) are included in a number of herbal remedies for a variety of ailments of probable microbial origin. Using a filter disk assay, plain and heated aqueous extracts from fresh Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens varieties were tested for their antimicrobial effects with fifteen bacterial species and one yeast species. Two pungent compounds found inCapsicum species (capsaicin and dihydrocapsaicin) were also tested for their antimicrobial effects. The plain and heated extracts were found to exhibit varying degrees of inhibition against Bacillus cereus, Bacillus subtilis, Clostridium sporogenes, Clostridium tetani, and Streptococcus pyogenes.Source:
Robert H. Cichewicz, Patrick A. Thorpe. Journal of EthnopharmacologyVolume 52, Issue 2, June 1996, Pages 61–70. doi:10.1016/0378-8741(96)01384-0http://www.sciencedirect.com/science/article/pii/0378874196013840

Carbomer

The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro
Abstract
Two mucoadhesive polymers, chitosan-glutamate and carbomer, were studied in an in vitro model (Caco-2 cell monolayers) with respect to their ability to enhance intestinal peptide drug delivery. Preparations of the polymers at concentrations of 0.5, 1.0, and 1.5% w/v (chitosan), and of 0.5 and 1.0% w/v (carbomer) were applied to the apical side of Caco-2 cell monolayers. The effects on transepithelial electrical resistance (TEER), paracellular transport of a FITC-dextran of a molecular weight of 4400 (FD-4) and [14C]mannitol were measured. Paracellular transport of FD-4 was visualized by means of confocal laser scanning microscopy (CLSM). Furthermore, the impact of lowering the pH of the polymer solutions to pH 4 on the integrity of the cell layer was determined. The results show that both polymers were able to decrease TEER of Caco-2 cell layers significantly. In the case of carbomer, CLSM revealed a partial opening of epithelial tight junctions. Lowering of the pH in the control and polymer solutions to pH 4 resulted in every case in the irreversible damage of a large percentage of the cells, as shown by CLSM. Transport studies with [14C]mannitol and FD-4 showed only during co-application of carbomer significantly increased fluxes, whereas no difference from the control solution could be detected for chitosan-glutamate. A threshold value of about 50% of TEER reduction has been identified, which allows for transport of hydrophilic compounds across the cell monolayers of the Caco-2 cell model.Source:
Gerrit Borchard, Henrik L. Lueβen, Albertus G. de Boer, J.Coos Verhoef, Claus-M. Lehr, Hans E. Junginger. Journal of Controlled Release Volume 39, Issues 2–3, May 1996, Pages 131–138. doi:10.1016/0168-3659(95)00146-8http://www.sciencedirect.com/science/article/pii/0168365995001468

Cytoprotective effects of Hyaluronic Acid and Carbomer 934P in Ocular Surface Epithelial Cells
Abstract:
To investigate in vitro the cell toxicity and antioxidant effects of two major tear substitutes, hyaluronic acid and a widely used carbomer, with and without preservative.
Chang conjunctival cells were treated with different concentrations of unpreserved or preserved carbomer 934P (0.03% and 0.3%), unpreserved or preserved hyaluronic acid (0.018% and 0.18%), and benzalkonium chloride (BAC 0.0005% and 0.005%) for 15 minutes or for 15 minutes with 24 hours of cell recovery, according to previously validated methods. Microplate cold light cytofluorometry was performed to evaluate cell viability (neutral red test), chromatin condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests). Confocal microscopy was used to explore morphologic changes.
No alterations were found with unpreserved and preserved hyaluronic acid at all concentrations and times tested. A decrease in cell viability with chromatin condensation appeared with 0.3% preserved carbomer 934P at the two times tested. This cytotoxicity, however, was significantly less than that observed with BAC alone, although the same concentrations of preservative were used. Unpreserved carbomer 934P induced no modification of cell viability after 15 minutes but a significant decrease in chromatin condensation, reversible after 24 hours of cell recovery, when a delayed decrease in cell viability was observed. Production of reactive oxygen species (ROS) decreased with the four formulations of tear substitutes tested at their usual concentrations, whereas a significant production of ROS occurred with BAC.
These two ophthalmic hydrogels have no cytotoxicity but possess antioxidant properties and tend to reduce the toxic effects of preservatives. These results may allow use of hydrogels, not only in dry eye but also in ocular surface disorders involving oxidative stress and in ophthalmic drug therapy to improve ocular tolerance.Source:
Cellular Pharmacotoxicology Unit, Toxicology Laboratory, Quinze-Vingts, National Hospital Center for Ophthalmology, Ambroise Paré AP-HP, University of Paris-V, Paris, France.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.66). 12/2002; 43(11):3409-15.

Temoporfin-loaded liposomal gels: Viscoelastic properties and in vitro skin penetration
Abstract
Temoporfin (mTHPC) is a potent second-generation photosensitizer. The primary object of this study was to develop a topical mTHPC-loaded liposomal hydrogel able to deliver mTHPC into the stratum corneum (SC) and deeper skin layers. This study was conducted (1) to determine the effect of carbomer concentration, used as a gelling agent, and the effect of phosphatidylcholine (PC) content of lecithin, used for the liposome preparation, on viscoelastic properties and viscosity of liposomal gels and (2) to determine the relationship between rheological properties of gels and the skin penetration of mTHPC. Liposomal hydrogels revealed plastic flow behaviour. The increase of carbomer concentration induced a domination of elastic over viscous behaviour of gels. There was an inverse relationship between the elasticity of gels and mTHPC-penetration. Viscosity also increased with the increment of carbomer concentration, reducing the mTHPC-penetration. Liposomal gels containing lecithin of smaller PC-content (i.e. smaller purity) exhibited a more elastic solid behaviour than gels containing lecithin with high PC-content, and showed smaller mTHPC-penetration. The gel containing 0.75%, w/w, carbomer and lecithin with high PC-content was considered to be the optimal formulation, since it delivered high amounts of mTHPC to the SC and deeper skin layers, and it possessed desirable rheological properties.Source:
Temoporfin-loaded liposomal gels: Viscoelastic properties andin vitro skin penetration. Nina Dragicevic-Curic, Sven Winter, Mirjana Stupar, Jela Milic, Danina Krajišnik, Burkhard Gitter, Alfred Fahr. International Journal of Pharmaceutics. Volume 373, Issues 1–2, 21 May 2009, Pages 77–84

Xanthan gum biosynthesis and application: a biochemical /genetic perspective
Abstract:
Xanthan gum is a complex exopolysaccharide produced by the plant-pathogenic bacteriumXanthomonas campestris pv. campestris. It consists of D-glucosyl, D-mannosyl, and D-glucuronyl acid residues in a molar ratio of 2:2:1 and variable proportions of O-acetyl and pyruvyl residues. Because of its physical properties, it is widely used as a thickener or viscosifier in both food and non-food industries. Xanthan gum is also used as a stabilizer for a wide variety of suspensions, emulsions, and foams. This article outlines aspects of the biochemical assembly and genetic loci involved in its biosynthesis, including the synthesis of the sugar nucleotide substrates, the building and decoration of the pentasaccharide subunit, and the polymerization and secretion of the polymer. An overview of the applications and industrial production of xanthan is also covered.Source:
Xanthan gum biosynthesis and application: a biochemical /genetic perspective. A. Becker,F. Katzen, A. Pühler, L. Ielpi. Applied Microbiology and Biotechnology. August 1998, Volume 50, Issue 2, pp 145-152.http://link.springer.com/article/10.1007/s002530051269

Intermolecular binding of xanthan gum and carob gum
Abstract.
Gels are a representative state for polysaccharides in both natural and artificial systems. The nature of the inter-chain associations within the junction zones is important and models for such interactions between like polysaccharides are based on X-ray diffraction studies of oriented gels. Here we describe the extension of such studies to a binary gel (xanthan-carob) in order to characterize for the first time intermolecular binding between different polysaccharides. Xanthan-carob binding has been proposed to explain gelation of the mixtures and as a model for host-pathogen recognition and adhesion of Xanthomonas bacteria within plant vascular systems. Our data suggest that the established model1–7 is incorrect and point to an alternative association mechanism.

Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour..
Abstract:
A comparative investigation has been undertaken to assess the performance of xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) as hydrophilic matrix-forming agents in respect of compaction characteristics and in vitro drug release behaviour. The overall compaction characteristics are found to be quite similar to each other and typical of polymer behaviour. But the flow characteristics are different, i.e., XG is more readily flowable than HPMC. The observed difference in drug release profiles between these two potential excipients are explored and explained by the difference in their hydrophilicity and subsequent hydration properties.Source:
Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour. Mohammad Mahiuddin Talukdar, Armand Michoel, Patrick Rombaut, Renaat Kinget. International Journal of Pharmaceutics.Volume 129, Issues 1–2, 8 March 1996, Pages 233–241. doi:10.1016/0378-5173(95)04355-1

Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography
Abstract
A reversed-phased HPLC method that allows the separation and simultaneous determination of the preservatives benzoic (BA) and sorbic acids (SA), methyl- (MP) and propylparabens (PP) is described. The separations were effected by using an initial mobile phase of methanol–acetate buffer (pH 4.4) (35:65) to elute BA, SA and MP and changing the mobile phase composition to methanol–acetate buffer (pH 4.4) (50:50) thereafter. The detector wavelength was set at 254 nm. Under these conditions, separation of the four components was achieved in less than 23 min. Analytical characteristics of the separation such as limit of detection, limit of quantification, linear range and reproducibility were evaluated. The developed method was applied to the determination of 67 foodstuffs (mainly imported), comprising soft drinks, jams, sauces, canned fruits/vegetables, dried vegetables/fruits and others. The range of preservatives found were from not detected (nd)—1260, nd—1390, nd—44.8 and nd—221 mg kg−1 for BA, SA, MP and PP, respectively.
Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography.Source:
Bahruddin Saad,Md. Fazlul Bari, Muhammad Idiris Saleh, Kamarudzaman Ahmad, Mohd. Khairuddin Mohd. Talib. Journal of Chromatography A. Volume 1073, Issues 1–2, 6 May 2005, Pages 393–397. 28th International Symposium on High Performance Liquid Phase Separations and Related Techniques. HPLC 2004. doi:10.1016/j.chroma.2004.10.105

3 Final Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, and Butylparaben
Abstract:
The Parabens are esters of p-hydroxybenzoic acid (PHBA) and are the most commonly used as preservatives in cosmetic formulations. Data obtained from chronic administration studies indicate that Parabens are rapidly absorbed, metabolized, and excreted.
Acute chronic and subchronic toxicity studies in animals indicate that Parabens are practically nontoxic by various routes of administration. Methylparaben and Ethylparaben at 100 percent concentration were slightly irritating when instilled into the eyes of rabbits.
Numerous in vitro mutagenicity studies indicate that the Parabens are non-mutagenic. Methylparaben was noncarcinogenic when injected in rodents or when administered intravaginally in rats. Cocarcinogenesis studies on Propyl- and Methylparaben were negative. Teratogenic studies on Methyl- and Ethylparaben were also negative.
Parabens are practically nonirritating and nonsensitizing in the human population with normal skin. Paraben sensitization has been reported when Paraben-containing medicaments have been applied to damaged or broken skin. Photo-contact sensitization and phototoxicity tests on product formations of Methyl-, Propyl-, and/or Butylparaben gave no evidence of significant photoreactivity.
It is concluded that Methylparaben, Ethylparaben, Propylparaben, and Butylparaben are safe as cosmetic ingredients in the present practices of use.Source:
3 Final Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, and Butylparaben. . International Journal of ToxicologySeptember/October 1984 vol. 3 no. 5147-209. doi: 10.3109/10915818409021274

Methylparaben potentiates UV-induced damage of skin keratinocytes.
Abstract:
For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24 h, exposed to UVB (15 or 30 mJ/cm2) and further cultured for another 24 h. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. Oxidative stress, nitric oxide (NO) production and cellular lipid peroxidation were measured using fluorescent probes. In addition, activation of nuclear factor kappa B and activator protein-1 was assessed by electro-mobility gel-shift assay. Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, NO production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.Source:
Methylparaben potentiates UV-induced damage of skin keratinocytes. Osamu Handa, Satoshi Kokura, Satoko Adachi, Tomohisa Takagi, Yuji Naito, Toru Tanigawa, Norimasa Yoshida,Toshikazu Yoshikawa.Toxicology. Volume 227, Issues 1–2, 3 October 2006, Pages 62–72. doi:10.1016/j.tox.2006.07.018

Propyl Paraben

Skin Permeation of Parabens in Excised Guinea Pig Dorsal Skin, Its Modification by Penetration Enhancers and Their Relationship with n-Octanol/Water Partition Coefficients
Abstract
Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol, ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butyl paraben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of the hydrophiic paraben.Source:
Shuji KITAGAWA, Hui LI, Shinji SATO. Chemical and Pharmaceutical Bulletin. Vol. 45 (1997) No. 8 P 1354-1357. http://doi.org/10.1248/cpb.45.1354https://www.jstage.jst.go.jp/article/cpb1958/45/8/45_8_1354/_article

RELEASE OF PROPYL PARABEN FROM A POLYMER COATING INTO WATER AND FOOD SIMULATING SOLVENTS FOR ANTIMICROBIAL PACKAGING APPLICATIONS.
Abstract:
The release phenomena of propyl paraben from a polymer coating to water and three food simulating solvents (10% aqueous ethanol, 50% aqueous ethanol, n-heptane) were studied for antimicrobial packaging applications. The effects of food simulating solvent, initial concentration in the coating and temperature on the propyl paraben release were examined. The initial concentration of propyl paraben in the coating ranged from 1.26 × 104 to 10.52 × 104 g/m3 and the temperature from 5.5 to 30C. For water, the release was controlled by Fickian diffusion with constant diffusion coefficient (7±11 × 10-11 cm2/s at 30C), and independent of the initial concentration. For 10% ethanol, the release followed again the Fickian model with constant diffusion coefficient (30±40 × 10-11 cm2/s at 30C). For 50% ethanol and n-heptane, the release was instantaneous and not controlled by Fickian diffusion. For the release into water, the activation energy for diffusion from the Arrhenius relationship was around 88 kJ/mole.Source:
RELEASE OF PROPYL PARABEN FROM A POLYMER COATING INTO WATER AND FOOD SIMULATING SOLVENTS FOR ANTIMICROBIAL PACKAGING APPLICATIONS. DONGHWAN CHUNG, SPYRIDON E. PAPADAKIS and KIT L. YAM. Journal of Food Processing and Preservation. Volume 25, Issue 1, pages 71–87, April 2001. DOI: 10.1111/j.1745-4549.2001.tb00444.x

Safety assessment of propyl paraben: a review of the published literature.
Abstract
Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the gastrointestinal tract and dermis. It is hydrolyzed to p-hydroxybenzoic acid, conjugated and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that propyl paraben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-effect levels (NOEL) as high as 1200–4000 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5–15% in patch testing are needed to elicit reaction in susceptible individuals. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.Source:
Safety assessment of propyl paraben: a review of the published literature M.G. Soni, G.A. Burdock,S.L. Taylor,N.A. Greenberg. Food and Chemical Toxicology. Volume 39, Issue 6, June 2001, Pages 513–532. doi:10.1016/S0278-6915(00)00162-9

Jojoba Oil

Jojoba oil wax esters and derived fatty acids and alcohols: Gas chromatographic analyses
Abstract
HCl-catalyzed ethanolysis followed by saponification readily surmounts the resistance of long chain wax esters to direct hydrolysis by alkali. Additionally, choosing ethyl instead of methyl esters allows baseline separations between long-chain alcohols and corresponding esters in gas liquid chromatographic (GLC) analysis of total alcohol and acid components before saponification. Liquid wax esters were analyzed on a temperature-programmed 3% OV-1 silicone column. Geographical and genetic effects on the variability of jojoba oil composition were investigated with five different seed samples. Major constituents in jojoba seed oil from shrubs in the Arizona deserts, as indicated by GLC analyses of oil, ethanolysis product, isolated fatty alcohols and methyl esters of isolated fatty acids, were C40 wax ester 30%, C42 wax ester 50% and C44 wax ester 10%; octadecenoic acid 6%; eicosenoic acid 35%, docosenoic acid 7%, eicosenol 22%, docosenol 21% and tetracosenol 4%. Oil from smaller leaved prostrate plants growing along California’s oceanside showed a slight tendency toward higher molecular size than oils from the California desert and Arizona specimens. The wax esters are made up of a dispro-portionately large amount of docosenyl eicosenoate and are not a random combination of constituent acids and alcohols.Lunaria annua synthetic wax ester oil was used as a model for evaluating the analytical procedures.Source:Thomas K. Miwa, Journal of the American Oil Chemists Society June 1971, Volume 48, Issue 6, pp 259-264. DOI 10.1007/BF02638458http://link.springer.com/article/10.1007/BF02638458

Skin nonpenetrating sunscreens for cosmetic and pharmaceutical formulations.
Abstract:
Ultraviolet (UV) solar radiation produces harmful effects on the skin including sunburn, local immunosuppression, skin photoaging, and cutaneous malignancies. Although application of sunscreens is the “gold standard” for protecting the skin from UV radiation, studies have shown that currently used sunscreens can cause adverse skin and systemic reactions, owing to their penetration into the viable cutaneous strata and to transdermal absorption. This paper presents new nonpermeating sunscreens (NPSUN) suitable for use in cosmetic and pharmaceutical products. The basic idea behind the design of the new photoprotectors was to immobilize UV-absorbing moieties in the Jojoba oil chemical backbone. The physicochemical characteristics of NPSUNs allow these derivatives to remain confined to the upper stratum corneum where the sunscreen molecule acts, with no further clearance to deeper dermal strata or systemic circulation. As an example, no permeation across the skin of methoxycinnamate-NPSUN was observed during 24-hour in vitro experiments, after topical application of either unformulated substances or of methoxycinnamate-NPSUNs formulated in oil-in-water cream, in water-in-oil cream, or in Jojoba oil. Another approach to increase the photoprotective effect against the UV radiation is targeting the delivery of α tocoperol into the deeper skin layers and across the cell membranes. This is necessary for optimal photoprotection and prevention of malignant processes. For this purpose, ethosomal vitamin E compositions were designed, characterized, and tested. Efficient intracellular and dermal accumulation of vitamin E from ethosomes was demonstrated.Source:
Skin nonpenetrating sunscreens for cosmetic and pharmaceutical formulations Elka Touitou, PhD, Biana Godin, PhD. Clinics in Dermatology. Volume 26, Issue 4, July–August 2008, Pages 375–379. doi:10.1016/j.clindermatol.2008.01.014

Solubilization of lycopene in jojoba oil microemulsion.
Abstract
The unique properties of jojoba oil make it an essential raw material in the manufacture of cosmetics. New, totally dilutable U-type microemulsions of water, jojoba oil, alcohols, and the nonionic surfactant polyoxyethylene-10EO-oleyl alcohol (Brij 96V) have been formulated recently. Here, these microemulsions are shown to be capable of solubilizing lycopene, a nutraceutical insoluble in water and/or oil, much more effectively than the solvent (or a solvent and surfactant blend) can dissolve them. In water-in-oil (W/O) and oil-in-water (O/W) microemulsions with 10 and 90 wt% water, respectively, the normalized maximal solubilization efficiency α is ca. 20-fold larger than its solubility. The solubilization capacity of the system is mainly surfactant-concentration dependent. The lycopene resides at the interfaces of the W/O and O/W microemulsions and engenders significant structural changes in the organization of the microemulsion droplets. In the absence of lycopene, the droplets are spherical; when lycopene is added, compaction of the droplets and formation of threadlike droplets are observed. On further addition of lycopene, the bridging effect wanes and the droplets revert to a spherical shape. The enhanced solubilization demonstrated for lycopene opens up new options for formulators interested in making liquid and transparent products for cosmetic or pharmaceutical uses..

Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation.
Abstract
Orange peel oil has previously been shown to be a promoter of mouse skin tumors. It has been assumed that this activity is due to its major (95%) constituent, d-limonene. We have tested both orange peel oil and purified d-limonene as skin tumor promoters in a two-stage skin carcinogenesis model in which tumors were initiated with 7, 12-dimethylbenz[a]-anthracene. We confirmed that topically applied orange peel oil is a very weak promoter of both skin papillomas and carcinomas. However, this promotional activity could not be accounted for by topically applied d-limonene. We thus feel that one or more minor components of orange peel oil has promotional activity. Neither orange peel oil nor d-limonene had promotional activity when given via the diet.Source:
Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation. J.Abiodun Elegbede, Terese H. Maltzman, Ajit K. Verma, Martin A. Tanner, Charles E. Elson and Michael N. Gould, Carcinogenesis (1986) 7 (12):2047-2049. doi: 10.1093/carcin/7.12.2047

Citrus Peel Use Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Skin.
Abstract:
Limonene has demonstrated efficacy in preclinical models of breast and colon cancers. The principal sources of d-limonene are the oils of orange, grapefruit, and lemon. The present case-control study was designed to determine the usual citrus consumption patterns of an older Southwestern population and to then evaluate how this citrus consumption varied with history of squamous cell carcinoma (SCC) of the skin. In this Arizona population, 64.3% and 74.5% of the respondents reported weekly consumption of citrus fruits and citrus juices, respectively. Orange juice (78.5%), orange (74.3%), and grapefruit (65.3%) were the predominant varieties of citrus consumed. Peel consumption was not uncommon, with 34.7% of all subjects reporting citrus peel use. We found no association between the overall consumption of citrus fruits [odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.73-1.32] or citrus juices (OR = 0.97, 95% CI = 0.71-1.31) and skin SCC. However, the most striking feature was the protection purported by citrus peel consumption (OR = 0.66, 95% CI = 0.45-0.95). Moreover, there was a dose-response relationship between higher citrus peel in the diet and degree of risk lowering. This is the first study to explore the relationship between citrus peel consumption and human cancers. Our results show that peel consumption, the major source of dietary d-limonene, is not uncommon and may have a potential protective effect in relation to skin SCC. Further studies with large sample sizes are needed to more completely evaluate the interrelationships between peel intake, bioavailability of d-limonene, and other lifestyle factors.Source:
Citrus Peel Use Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Skin. Iman A. Hakim, Robin B. Harris & Cheryl Ritenbaugh. Nutrition and Cancer. Volume 37, Issue 2, 2000. pages 161-168. DOI: 10.1207/S15327914NC372_7

Lemon Oil

Oxidized citrus oil (R-limonene): A frequent skin sensitizer in Europe
Background: Peel oil from citrus fruits consists of R-(+)-limonene, which is one of the most commonly used fragrance materials in technical products and in fine fragrances. This substance forms allergenic oxidation products during handling and storage.Objective: We wanted to study the frequency of allergic reactions to oxidized R-(+)-limonene in patients with dermatitis and find a suitable test preparation. Method: Patch testing with oxidized R-(+)-limonene was performed on 2273 patients at 4 dermatology clinics in Europe. Results: Of the consecutive patients tested, 3.8% to 3.9% had positive reactions in two of the clinics; 6.5% had positive reactions in the third clinic; and 0.3% had positive reactions in the fourth clinic. A total of 63 patients showed positive reactions. In total, 57% of the patients did not react to fragrance mix or balsam of Peru. We recommend testing with 3% oxidized R-(+)-limonene in patients referred for patch testing. Conclusion: The high frequency of oxidized limonene allergy provides clinical evidence for the European classification of R-(+)-limonene that contains oxidation products as skin sensitizers. (J Am Acad Dermatol 2002;47:709-14.)Source:
Mihály Matura, MD, PhDa, An Goossens, RPharm, PhDb, Olivia Bordalo, MDc,Begoña Garcia-Bravo, MDd, Kerstin Magnussona Karin Wrangsjö, MD, PhDe, Ann-Therese Karlberg, RPharm, PhDa. Journal of the American Academy of Dermatology. Volume 47, Issue 5, November 2002, Pages 709–714. doi:10.1067/mjd.2002.124817http://www.sciencedirect.com/science/article/pii/S0190962202001500

A study of the phototoxicity of lemon oil
Summary
Lemon oil contains furocoumarin derivatives and is known to cause phototoxicity. In this study, lemon oil was fractionated, and its phototoxic activity was measured by means of a biological assay. The substances producing phototoxicity were identified by high-performance liquid chromatography as being oxypeucedanin and bergapten. The phototoxic potency of oxypeucedanin was only one-quarter of that of bergapten. However, the amounts of these two phototoxic compounds present in lemon oils produced in different regions of the world varied by a factor of more than 20 (bergapten, 4–87 ppm; oxypeucedanin, 26–728 ppm), and their ratio was not constant. The two compounds accounted for essentially all of the phototoxic activity of all lemon-oil samples. Among various other citrus-essential oils investigated, lime oil and bitter-orange oil also contained large amounts of oxypeucedanin. Oxypeucedanin was found to elicit photopigmentation on colored-guinea-pig skin without preceding visible erythema.Source:
A study of the phototoxicity of lemon oil. M. Naganuma, S. Hirose, Y. Nakayama, K. Nakajima, T. Someya. Archives of Dermatological Research. October 1985, Volume 278, Issue 1, pp 31-36.http://link.springer.com/article/10.1007/BF00412492

Biochemical studies on a novel antioxidant from lemon oil and its biotechnological application in cosmetic dermatology.
Abstract
It is generally accepted that lipid peroxides play an important role in the pathogenesis of free radical-induced cellular injury and that antioxidants such as glutathione, ascorbic acid and alpha-tocopherolare vital in cellular defense against endogenous and exogenous oxidants. The purpose of this study was to investigate the effectiveness of a natural compound, derived from lemon oil extract, in controlling free radical-induced lipid peroxidation and tissue damage in the skin. We provide evidence that a compound isolated from lemon oil, which we have called Lem1, is endowed with a strongantioxidant activity and that it is capable of inhibiting free radical-mediated reactions, evaluated by both in vitro and in vivo biochemical systems. The present study aims to give a preclinical perspective on the biochemical properties of Lem1, a natural compound, as well as to provide a better understanding of the endogenous antioxidant potential of skin and the real validity of a natural antioxidant biotechnology in the antiaging management of the skin.Source:
Biochemical studies on a novel antioxidant from lemon oil and its biotechnological application in cosmetic dermatology. Calabrese V, Randazzo SD, Catalano C, Rizza V. Faculty of Medicine, Dept. of Chemistry, University of Catania, Italy. Calabrese@mbox.Unict.It. Drugs Under Experimental and Clinical Research [1999, 25(5):219-225]http://europepmc.org/abstract/med/10568210

Oxidative stress and antioxidants at skin biosurface: a novel antioxidant from lemon oil capable of inhibiting oxidative damage to the skin.
Abstract
Atmospheric pollutants are an important source of oxidative and nitrosative stress both to terrestrial plants and to animals. Skin, which has a highly differentiated and certainly complex organizational structure, is particularly vulnerable to free radical damage because of its contact with oxygen and with other environmental stimuli. Fruit and vegetables contain several classes of compounds that when ingested can potentially contribute to antioxidant defenses. In the present study we employed a novel gas chromatographic method to assess the antioxidant properties of a natural compound isolated fromlemon oil, which we have called Lem1. We provide experimental evidence that Lem1 is endowed with a strong antioxidant activity and that it is capable of inhibiting free radical-mediated reactions, as evaluated in vitro and in vivo. The present study extends our previous findings and demonstrates that topical application of Lem1 in healthy volunteers significantly increases the antioxidative potential of skin biosurface, thus highlighting the effectiveness of a natural antioxidant biotechnology in the antiaging management of skin.Source:
Calabrese V, Scapagnini G, Randazzo SD, Randazzo G, Catalano C, Geraci G, Morganti P. Faculty of Medicine, Department of Chemistry, University of Catania, Italy. Calabrese@mbox.Unict.it. Drugs Under Experimental and Clinical Research [1999, 25(6):281-287].http://europepmc.org/abstract/med/10713866

Grapefruit Oil

Oxidative stress and antioxidants at skin biosurface: a novel antioxidant from lemon oil capable of inhibiting oxidative damage to the skin.
Abstract
Atmospheric pollutants are an important source of oxidative and nitrosative stress both to terrestrial plants and to animals. Skin, which has a highly differentiated and certainly complex organizational structure, is particularly vulnerable to free radical damage because of its contact with oxygen and with other environmental stimuli. Fruit and vegetables contain several classes of compounds that when ingested can potentially contribute to antioxidant defenses. In the present study we employed a novel gas chromatographic method to assess the antioxidant properties of a natural compound isolated from lemon oil, which we have called Lem1. We provide experimental evidence that Lem1 is endowed with a strong antioxidant activity and that it is capable of inhibiting free radical-mediated reactions, as evaluated in vitro and in vivo. The present study extends our previous findings and demonstrates that topical application of Lem1 in healthy volunteers significantly increases the antioxidative potential of skin biosurface, thus highlighting the effectiveness of a natural antioxidant biotechnology in the antiaging management of skin.Source:Calabrese V,Scapagnini G,Randazzo SD,Randazzo G,Catalano C,Geraci G,Morganti PDrugs Under Experimental and Clinical Research [1999, 25(6):281-287]http://europepmc.org/abstract/med/10713866

Coumarins and psoralens in grapefruit peel oil.
Abstract
Four coumarins, four psoralens and two methoxyflavones were isolated and identified from the peel oil of grapefruit. Five of these compounds are reported as constituents of grapefruit oil for the first time, one of which, 5[(3,7-dimethyl-6-epoxy-2-octenyl) oxy]psoralen is a new natural product.Source:
Coumarins and psoralens in grapefruit peel oil. James H. Tatum, Robert E. Berry. Phytochemistry. Volume 18, Issue 3, 1979, Pages 500-502. doi:10.1016/S0031-9422(00)81903-2.

Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)
Abstract
Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed.
In this in vivo study with the rat, we have investigated the hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.)
After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E.
After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%.
The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model.
The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.

Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied.
The skin of the skh-1 mouse after ultraviolet B (280-320 nm, UVB) irradiation shows the pathological changes typical of sunburn damage: spongiosis (edematous spaces) around some cells, necrosis of keratinocytes, giving rise to sunburn cells, inflammatory infiltration of polymorphonuclear leucocytes, etc. In our previous study, these were accompanied by erythema, increased skin sensitivity, andedematous swelling. The topical application of tocopherol acetate (TA) immediately after the UVB exposure decreased these changes. In this paper, multiple measurements of the skin thickness were made at different locations along the magnetic resonance imaging (MRI) cross-sectional image of the skin. This permits effects to be quantified with (if desired) the contralateral half of the back serving as an internal control, either exposed (positive control) or unexposed (negative control). Topical application of TA resulted in an increase in the concentration of free tocopherol in the skin. No qualitative differences in ultrastructural appearance of the UVB-irradiated, TA-treated skin could be discerned by careful examination. In vivo high resolution video microscopy of blood flow in venules of the irradiated mouse ear revealed a large (tenfold) but not statistically significant decrease in stationary lymphocytes adhering to the venule walls. The delaying of the application of TA up to 8 hours after the termination of UVB irradiation still offered statistically significant protection as did immediate application of 5% TA in diluent Myritol 318 (Delios S, Henkel).Source:
Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied.Trevithick JR, Shum DT, Redae S, Mitton KP, Norley C, Karlik SJ, Groom AC, Schmidt EE. Department of Biochemistry, Faculty of Medicine, University of Western Ontario, London, Canada. Scanning Microscopy [1993, 7(4):1269-1281]http://europepmc.org/abstract/med/8023094

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.
Abstract:
Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115–0.23 J/cm2 results after 24–48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-α-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40–55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel noninvasive technique not previously reported for this purpose—magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p < 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p < 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p < 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible 0even after the irradiation has stopped, by a derivative of d-α-tocopherol which is stable to autooxidation.Source:
Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. John R. Trevithick, Hua Xiong, Shirley Lee, David T. Shum, S.Ernest Sanford, Stephen J. Karlik , Christopher Norley, Geoffrey R. Dilworth. Archives of Biochemistry and Biophysics. Volume 296, Issue 2, 1 August 1992, Pages 575-582. doi:10.1016/0003-9861(92)90613-2

Retinyl Palmitate (Vitamin A)

Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin
Abstract
To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6–24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice
Abstract
Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4–6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for the ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.
Sources:
Z. Malik, G. Kostenich, L. Roitman, B. Ehrenberg, A. OrensteinJournal of Photochemistry and Photobiology B: BiologyVolume 28, Issue 3, June 1995, Pages 213–218. doi:10.1016/1011-1344(95)07117-Khttp://www.sciencedirect.com/science/article/pii/101113449507117K

Lexaminopeptide complex

Synthesis and Biological Evaluation in Vitro of Selective, High Affinity Peptide Antagonists of Human Melanin-Concentrating Hormone Action at Human Melanin-Concentrating Hormone Receptor 1
Abstract
Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of Ac-Arg6-cyclo(S−S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13-Arg14-Pro15-Cys16)-NH2, a high affinity but nonselective agonist at hMCH-1R and hMCH-2R, were prepared and tested in binding and functional assays on cells expressing these receptors. In the new analogues, 5-aminovaleric acid (Ava) was incorporated in place of the Leu9-Gly10 and/or Arg14-Pro15 segments of the disulfide ring. Several of these compounds turned out to be high affinity antagonists selective for hMCH-1R. Moreover, even at micromolar concentrations, they were devoid of agonist potency at both hMCH receptors and not effective as hMCH-2R antagonists. For example, peptide 14, Gva6- cyclo(S−S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13-Ava14,15−Cys16)-NH2, (Gva = 5-guanidinovaleric acid), was a full competitive hMCH-1R antagonist (IC50 = 14 nM, KB = 0.9 nM) with more than 1000-fold selectivity over hMCH-2R. Examination of various compounds with Ava in positions 9,10 and/or 14,15 revealed that the Leu9-Gly10 and Arg14-Pro15 segments of the disulfide ring are the principal structural elements determining hMCH-1R selectivity and ability to act as a hMCH-1R antagonist.Source:
Maria A. Bednarek , Donna L. Hreniuk , Carina Tan , Oksana C. Palyha , Douglas J. MacNeil , Lex H. Y. Van der Ploeg , Andrew D. Howard , and Scott D. Feighner. Journal of Medicinal Chemistry , Biochemistry, 2002, 41 (20), pp 6383–6390. DOI: 10.1021/bi0200514http://pubs.acs.org/doi/abs/10.1021/bi0200514

What our customers say…

Real People, Real Results.

“It does work … I don’t see myself not using this product every day.“

*results not typical

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It does work … I don’t see myself not using this product every day and can’t wait to see how my skin will continually improve. My only suggestion would be that the jars are larger because you literally want to dip yourself in this cream from head to toe and it doesn’t last long enough.
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“Feedback on my first day to try out ALLURE.”

*results not typical

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*results not typical

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“It’s the only product that really helps my skin look better and minimizes the appearance of sun damage, thanks.”*

*DISCLAIMER: Testimonials appearing on this site are actually received from actual customers. They are individuals’ experiences, reflecting real life experiences of those who have used our products in some way or another. However, they are individual results and results do vary. We do not claim that they are typical results that consumers will generally achieve. The testimonials are not necessarily representative of all those who will use our product. Additionally, these testimonials are not intended to make claims that these products can be used to diagnose, treat, cure, mitigate, or prevent any disease. These claims have not been clinically proven or evaluated by the FDA. The testimonials displayed are given verbatim except for correction of grammatical or typing errors. Some have been shortened. In other words, not the whole message received by the testimonial writer is displayed, when it seemed lengthy or not the whole testimonial seemed relevant for the general public.

*DISCLAIMER: Testimonials appearing on this site are actually received from actual customers. They are individuals’ experiences, reflecting real life experiences of those who have used our products in some way or another. However, they are individual results and results do vary. We do not claim that they are typical results that consumers will generally achieve. The testimonials are not necessarily representative of all those who will use our product. Additionally, these testimonials are not intended to make claims that these products can be used to diagnose, treat, cure, mitigate, or prevent any disease. These claims have not been clinically proven or evaluated by the FDA. The testimonials displayed are given verbatim except for correction of grammatical or typing errors. Some have been shortened. In other words, not the whole message received by the testimonial writer is displayed, when it seemed lengthy or not the whole testimonial seemed relevant for the general public.

FREQUENTLY ASKED QUESTIONS (FAQs)

Q: What is ALLURE LIFTING FIRMING CREAM?

• ALLURE CREAM contains natural ingredients to reduce your fine lines and wrinkle depth, lift your saggy skin, tighten, strengthen, and safeguard your pores, revitalize your age-impaired face and neck lines, wipe-out cellulite, boost your confidence, and leave you with the refreshed, restored glowing, virile, smooth, silky, sexy skin of your younger, happier, and healthier self. It’s a dermatologic cream used also for cellulites and as effective aging skin corrector. It is composed of dermatologically tested, backed by science, safe ingredients which are known to be very effective in enhancing skin’s natural glow and beauty. It promotes skin’s rejuvenation and protection. This gentle, smoothing cream formula is non-irritating. Perfect for men and women.

• ALLURE CREAM contains clinically proven ingredients will enhance the collagen production of the aging skin and will restore critical antioxidants that help rid your skin of free radicals which can cause premature aging in your skin. It will also promote skin rejuvenation and will recapture your youthful glow. ALLURE promotes cell regeneration, stimulates collagen, and improves elastin, firming and tightening skin for a smooth complexion.
Our customers report visible results in 2 to 4 weeks and results will continue to add up with regular use to improve skin tone and texture.
Among the ingredients included in ALLURE is the purest, cleanest, and most refreshing substance of all: Purified water: is a vital component of reducing bacteria’s ability to infect hosts by setting up colonies. As a result, we made sure the water going into ALLURE to help moisturize your skin was purified, increasing the nourishment your skin will receive.
Another essential ingredient included in ALLURE is Isopropyl Myristate, a commonly used acid we felt was instrumental in devising our breakthrough saggy skin corrector ALLURE. Isopropyl Myristate is most commonly applied when absorption through the skin is desired.
ALLURE also includes Stearyl Alcohol as one of its central ingredients. For years, Stearyl Alcohol has been used to help lubricate dry and sagging skin, helping give your skin the smooth, silky, and soft appearance it craves. In addition, ALLURE has been blended with a number of other effective ingredients such as Green Bean Extract, Orange Peel Oil, Lemon Oil, Tocopheryl Acetate or Vitamin E, Retinyl Palmitate or Vitamin A, and many, many more.
But that’s not all. We at PureHealth Research pride ourselves at going the extra mile to deliver a superior health-promoting product. This is why every bottle of ALLURE has been imbued with a super ingredient called PEG-100 Stearate, an effective solution made by combining natural oils such as palm or coconut with stearic acid to form a water-soluble ester. We made sure to include PEG-100 Stearate in our formula because this solution is instrumental in helping to clean skin and hair by helping water mix with oils and dirt in order to wash them away, giving your saggy skin the deep clean it needs before the epidermal barrier can be tightened up and smoothed over, resulting in the radiance you may not have experienced on your skin since your younger days.
These are just some of the effective, health-giving, skin-enhancing ingredients we’ve used in creating ALLURE: Firming Lifting Cream.

Q: How do I use ALLURE CREAM?

• Wash your body and apply to dried skin. Apply cream to skin wherever desired. Massage into skin using circular motions until absorbed. As product begins a mild warming feeling may occur. Apply ALLURE to your saggy skin two times per day (recommended). ALLURE can be applied first thing in the morning and right before you go to sleep. Apply during the day if needed. For external use only.

Q: Is it safe to apply to skin?

• ALLURE CREAM is clinically tested to be safe to apply not only on the face and neck area but the whole body skin as well. It has undergone thorough lab testing and ensured the highest quality of the product. Only the highest quality ingredients on the market were used in this hypoallergenic formula that is specially designed for sensitive, dry, oily, or normal skin types!

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• We suggest that it would be best to apply for those ages 30 years old and above.

Q: Is it for a short term use or long term use?

• For best results, since it is backed by science and safe, ALLURE CREAM is encouraged to be applied daily for continuous skin lifting and firming enhancement. Your skin will regain its natural barriers from regular daily abuse and return your skin to its former glory! ALLURE has been cultivated to deliver above and beyond your standard over-the-counter skin creams, and has been created to naturally lift and tighten your skin, removing wrinkles and cellulite, and improving the quality, vibrancy, and purity of your skin without subjecting yourself to costly and risky cosmetic surgeries.

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• It has been backed up with clinical studies and had been found to be perfectly safe to apply without any irritation. However, if irritation occurs, please discontinue application and consult your physician.

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PUREHEALTH RESEARCH ALLURE LIFTING FIRMING CREAMCLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:

Purified Water

Rapid enumeration of physiologically active bacteria in purified water used in the pharmaceutical manufacturing process
Abstract
Physiologically active bacteria in purified water used in the manufacturing process of pharmaceutical products were enumerated in situ. Bacteria with growth potential were enumerated using the micro-colony technique and direct viable counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean Casein Digest Broth) at 30 °C. Respiring and esterase-active bacteria were detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of bacteria in purified water retained physiological activity, while most could not form colonies on conventional media. The techniques applied in this study enabled bacteria to be counted within 24 h so results could be available within one working day. These rapid and convenient techniques should be useful for the systematic monitoring of bacteria in water used for pharmaceutical manufacturing.Source:
M. Kawai,N. Yamaguchi andM. Nasu.Journal of Applied Microbiology. Volume 86, Issue 3, pages 496–504, March 1999. DOI: 10.1046/j.1365-2672.1999.00689.xhttp://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.1999.00689.x/full

Isopropyl myristate is used in cosmetic and topical medicinal preparations where good absorption through the skin is desired.

Enhanced transdermal delivery of estradiol in vitro using binary vehicles of isopropyl myristate and short-chain alkanols

Abstract
The effect of binary vehicles of isopropyl myristate (IPM) and short-chain alkanols on the enhancement of skin permeation of estradiol (E2) was studied in vitro using human epidermal membrane. The steady-state fluxes of E2 and solvents across the skin were determined from saturated solutions of neat and binary solvents of IPM and ethanol (EtOH), n-propanol (n-PrOH), n-octanol (n-OcOH), or isopropanol (i-PrOH). While the neat solvents modestly increased the E2 flux, addition of IPM to the alkanols resulted in a synergistic enhancement of the E2 flux. Among the (1:1) binary cosolvents evaluated, i-PrOH produced the highest E2 flux (1.1 μg/cm2 per h), which was 35-fold greater than from water and over 15-fold greater than from the neat solvents. This combination was also the best in terms of relative compositions of the IPM/i-PrOH cosolvents. A strong correlation between E2 and i-PrOH fluxes suggested the enhancement for both permeants. While i-PrOH traversed the skin, IPM was retained in the stratum corneum. The uptake of both IPM and E2 in the stratum corneum was largely increased by adding i-PrOH (up to 50%) to IPM.Source:
Melinda Goldberg-Cettina,Puchun Liu, James Nightingale, Tamie Kurihara-Bergstrom.International Journal of Pharmaceutics.Volume 114, Issue 2, 14 February 1995, Pages 237–245. doi:10.1016/0378-5173(94)00253-2http://www.sciencedirect.com/science/article/pii/0378517394002532

Investigations into the formation and characterization of phospholipid microemulsions. I. Pseudo-ternary phase diagrams of systems containing water-lecithin-alcohol-isopropyl myristate
Abstract
Pseudo-ternary phase diagrams have been constructed for systems comprising of water-lecithin-alcohol-isopropyl myristate. Two types of lecithin were used in this study, namely soybean (Epikuron 200) and egg lecithin (Ovothin 200). Seven short chain alcohols (i.e., n-propanol, isopropanol, n-butanol, sec-butanol, isobutanol, tert-butanol and n-pentanol) were investigated as cosurfactants. In each system studied, a large monophasic, isotropic, non-birefringent area was seen to occur along the surfactant/oil axis; while at low oil concentrations, a second isotropic, non-birefringent area, usually associated with a liquid crystalline phase, was observed in many systems. Both isotropic regions were stable at room temperature at least for 3 months. Although no significant difference was observed between the phase diagrams produced by the two types of lecithin, the extent of the isotropic regions was dependent upon both the nature of the cosurfactant and lecithin/cosurfactant mixing ratio (Km).Source:
R. Aboofazeli, M.J. Lawrence. International Journal of Pharmaceutics. Volume 93, Issues 1–3, 31 May 1993, Pages 161–175.doi:10.1016/0378-5173(93)90174-E.http://www.sciencedirect.com/science/article/pii/037851739390174E

Investigations into the formation and characterization of phospholipid microemulsions. III. Pseudo-ternary phase diagrams of systems containing water-lecithin-isopropyl myristate and either an alkanoic acid, amine, alkanediol, polyethylene glycol alkyl ether or alcohol as cosurfactant
Abstract
The phase behaviour of quaternary systems composed of lecithin/isopropyl myristate/water/cosurfactant, at a lecithin: cosurfactant mixing ratio (Km) of 1:1 (on a weight basis) have been investigated by the construction of phase diagrams. The lecithin used in this study was the commercially available soybean lecithin, Epikuron 200 (purity greater than 94% phosphatidylcholine) and the cosurfactants examined were either short (alkyl chain length 4–6) straight-chain alkanoic acids, amines, alkanediols, diethylene glycol alkyl ethers or acohols. With the exception of the amines which appeared to react with lecithin, all the systems showed the area of existence of a stable isotropic region along the surfactant/oil axis (i.e., reverse microemulsion area; L2). In no case was a second isotropic region (i.e., normal microemulsion area; L1) observed, although in certain systems a single clear isotropic region covered virtually the whole of the phase diagram and may have included an L1 region. A liquid crystalline (LC) region was observed only in systems containing either an alkanediol or polyethylene glycol alkyl ether as cosurfactant. It was concluded that the area of existence of the various phase regions was very dependent upon the nature of the cosurfactant used.Source:
R. Aboofazeli, C.B. Lawrence, S.R. Wicks, M.J. Lawrence . International Journal of Pharmaceutics Volume 111, Issue 1, 6 October 1994, Pages 63–72. doi:10.1016/0378-5173(94)90402-2http://www.sciencedirect.com/science/article/pii/0378517394904022

Development of model membranes for percutaneous absorption measurements. I. Isopropyl myristate
Abstract
Studies have been conducted to test the validity of an in vitro model for percutaneous absorption in humans. The system consists of an artificial lipid membrane, which mimics the epidermal barrier, supported in a rotating diffusion cell. The artificial membrane was formed with isopropyl myristate (IPM), a lipid chosen to be representative of those in the stratum corneum. The membrane resistance to penetration has been studied for a range of compounds with diverse physicochemical properties. A positive correlation between transport resistance and the IPM-aqueous partition coefficient is demonstrated. The penetration data obtained from the artificial system are compared with those measured using excised human cadaver skin as the membrane in glass diffusion cells. A reasonable correlation was found between the resistances to diffusion provided by the IPM membrane and by excised skin, although the magnitude of the former was 1000-fold lower than of the latter. However, the IPM membrane did not predict the relatively low resistance of excised human skin to isoquinoline and nicotine. It is suggested that although the artificial membrane described provides a reasonable model for percutaneous absorption, modifications should be made to improve the predictability of the system.Source:
Jonathan Hadgraft, Geoffrey Ridout∗. International Journal of Pharmaceutics. Volume 39, Issues 1–2, September 1987, Pages 149–156. doi:10.1016/0378-5173(87)90210-9.http://www.sciencedirect.com/science/article/pii/0378517387902109

Effect of the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions on barrier properties of mice skin for transdermal permeation of tetracaine hydrochloride: In vitro
Abstract
Effect of composition of lecithin water-in-oil and oil-in-water microemulsion on in vitro transdermal permeation of tetracaine hydrochloride was studied on mice model. The results were compared with an aqueous solution of tetracaine hydrochloride (2.7 mg/ml). In vitro skin flux and permeability coefficients were obtained using the Franz diffusion cell. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) were used to study the mechanism of action of the microemulsion. Micrographs of TEM and CLSM studies were analyzed by using Image Pro Plus image software. Skin flux of tetracaine hydrochloride was found to be dependent on the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions. At lower Km ratio (i.e. 0.5:1 and 0.8:1) of microemulsion, the rate of permeation of tetracaine hydrochloride was higher when compared to the microemulsion of higher Km ratio (1:1 and 1.5:1). Image analysis of TEM micrograph, 6 h after application of lecithin microemulsion, showed 3.5 ± 0.75-fold (p < 0.001) increase in the intercellular space in the epidermis and 3.8 ± 0.4-fold (p < 0.001) enhancement in upper dermis. CLMS results show that sweat gland and hair follicles also provided path for permeation of the drug through the skin.Source:
Mohammad Changez ,Manoj Varshney, Jadish Chander, Amit Kumar Dinda. Colloids and Surfaces B: Biointerfaces. Volume 50, Issue 1, 1 June 2006, Pages 18–25. doi:10.1016/j.colsurfb.2006.03.018http://europepmc.org/abstract/MED/16690263

Structural characterisation of water–Tween 40®/Imwitor 308®–isopropyl myristate microemulsions using different experimental methods
Abstract
Pharmaceutically usable microemulsion systems were prepared from water and isopropyl myristate with a constant amount of Tween 40® and Imwitor 308® at a mass ratio of 1. Their type and structure were examined by measuring density and surface tension, and by viscometry, electric conductivity, differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS), and the degree of agreement between the techniques was assessed. A model based on monodisperse hard spheres adequately fits the SAXS data in W/O microemulsions predicting, depending on composition, elongated or spherical droplets. It also suggests the involvement of strong attractive interactions in O/W systems. Results of conductivity, viscosity, density and surface tension measurements confirm the prediction of a percolation transition to a bicontinuous structure. DSC detects the degree of water interaction with surfactants thus identifying the type of microemulsion. The conclusions from all the techniques agree well and indicate that such studies could also be carried out on more complex systems. In future, the ability to determine type and structure of such microemulsion systems could enable partitioning and release rates of drugs from microemulsions to be predicted.Source:
F Podlogar, M Gašperlin, M Tomšič, A Jamnik, M.Bešter Rogač. International Journal of Pharmaceutics. Volume 276, Issues 1–2, 19 May 2004, Pages 115–128. doi:10.1016/j.ijpharm.2004.02.018http://www.sciencedirect.com/science/article/pii/S0378517304001334

Influence of propylene glycol and isopropyl myristate on the in vitro percutaneous penetration of diclofenac sodium from carbopol gels
Abstract
The influence of propylene glycol (PG) on the in vitro penetration of diclofenac sodium (DFS) through a synthetic membrane and abdominal rat skin from carbopol gels was investigated using Franz-type diffusion cells. The combined effect of isopropyl myristate (IPM) and PG was also evaluated. It was found that the penetration through the synthetic membrane was well described by the Higuchi model. The gel containing 40% PG showed the highest release rate, indicating that a releasing maximum exists for PG content which provides the fully solubilized drug in the vehicle. When using rat skin as the barrier, the penetration rate was controlled by the membrane. DFS flux decreased with increasing PG content of the gels due to an increase of the drug affinity to the vehicle. A cosolvent action of PG was evident. However, the combination of PG and IPM resulted in a synergistic enhancement of DFS flux. Maximum enhancing activity was obtained from gels containing 40% PG, which yielded an enhancement ratio of about 8. Increasing IPM content from 3 to 5% increased the flux and decreased the lag time taken to reach a steady-state level.Source:
A. Arellano, S. Santoyo, C. Martı́n, P. Ygartua. European Journal of Pharmaceutical Sciences. Volume 7, Issue 2, 1 January 1999, Pages 129–135. doi:10.1016/S0928-0987(98)00010-4http://www.sciencedirect.com/science/article/pii/S0928098798000104

Effect of ethanol and isopropyl myristate on the availability of topical terbinafine in human stratum corneum, in vivo
Abstract
Purpose: The objective of this study was to determine the availability of the topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following its administration in formulations containing isopropyl myristate and ethanol. Methods: The ventral forearms of human volunteers were treated for 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl myristate (IPM), in ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period, the treated sites were carefully cleaned of excess vehicle and the SC was progressively removed by sequential tape stripping. TBF was quantified in the SC by: (a) extraction of the tape strips and subsequent HPLC analysis; and (b) attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each sequentially exposed SC surface during the tape stripping procedure. Results: The concentration profile of TBF in the SC (i.e. drug concentration as a function of depth in the membrane) was fitted to the appropriate solution of Fick’s second law of diffusion, allowing thereby the drug’s SC/vehicle partition coefficient (K) and characteristic diffusion parameter (D/L2, where D is the diffusivity of TBF in the SC of thickness L) to be deduced.Conclusions: While D/L2 for TBF derived from the three vehicles remained essentially constant, the drug’s partitioning into the SC was significantly higher from formulations containing ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC results supported these deductions.Source:
Ingo Alberti, Yogeshvar N Kalia, Aarti Naik, Jean-Daniel Bonny, Richard H Guy. International Journal of Pharmaceutics. Volume 219, Issues 1–2, 21 May 2001, Pages 11–19. doi:10.1016/S0378-5173(01)00616-0.http://www.sciencedirect.com/science/article/pii/S0378517301006160

Interfacial Composition and Thermodynamics of Formation of Water/Isopropyl Myristate Water-in-Oil Microemulsions Stabilized by Butan-1-ol and Surfactants Like Cetyl Pyridinium Chloride, Cetyl Trimethyl Ammonium Bromide, and Sodium Dodecyl Sulfate
The stabilization and destabilization of water-in-oil (w/o) microemulsion under varied amounts of surfactant and water and varied temperature by mixing with butan-1-ol and isopropyl myristate have been studied in detail. The surfactants used were sodium dodecyl sulfate, cetyl trimethyl ammonium bromide, and cetyl pyridinium chloride. The distribution of cosurfactant (butan-1-ol) between the interface and the oil at the threshold level of stability has been examined, and the thermodynamics of the transfer process of the cosurfactant from the oil to the interface have been evaluated. The structural parameters (dimension, population density, and water pool radius) of the dispersed water droplets in the oil phase have been also evaluated along with the examination of the interfacial population of surfactant and cosurfactant. A rational analysis of the results has been attempted.Source:
S. K. Hait and S. P. Moulik. Centre for Surface Science, Department of Chemistry, Jadavpur University, Calcutta 700 032, India. Langmuir, 2002, 18 (18), pp 6736–6744
DOI: 10.1021/la011504thttp://pubs.acs.org/doi/abs/10.1021/la011504t

Stearyl Alcohol

Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol help to form emulsions and prevent an emulsion from separating into its oil and liquid components. These ingredients also reduce the tendency of finished products to generate foam when shaken. When used in the formulation of skin care products, Stearyl Alcohol, Oleyl Alcohol and Octyldodecanol act as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.

Effect of cetostearyl alcohol on stabilization of oil-in-water emulsion: I. Difference in the effect by mixing cetyl alcohol with stearyl alcohol
Abstract
It is known that an oil-in-water emulsion increases in consistency and stability on addition of cetostearyl alcohol. When either cetyl alcohol or stearyl alcohol was added individually, the emulsion stability decreased. On storage at room temperature, unstable emulsions decreased in consistency and many particles (not visible immediately after preparation) appeared. The particles were determined to be crystals of the alcohol added. When both alcohols were included in the formulation simultaneously in the appropriate ratio, the emulsions were stable and did not show such changes. This difference in stability can be explained in relation to polymorphism of the alcohols.Source:
S Fukushima,M Takahashi,M Yamaguchi. Journal of Colloid and Interface Science
Volume 57, Issue 2, November 1976, Pages 201-206. doi:10.1016/0021-9797(76)90193-4http://www.sciencedirect.com/science/article/pii/0021979776901934

Contact Dermatitis From Stearyl Alcohol and Propylene Glycol in Fluocinonide Cream
Abstract
A young woman being treated for linear scleroderma became allergic to fluocinonide (Lidex) cream while using it with occlusion. She was able to continue treatment with fluocinonide ointment without an adverse reaction.
Patch testing with the ingredients of the cream demonstrated sensitization to an impurity in commercial stearyl alcohol and irritation from propylene glycol. The woman had no adverse reactions to fluocinonide ointment because this preparation contains no stearyl alcohol and very little propylene glycol.
This case reemphasizes the important role of vehicles in contact allergy and indicates that allergic sensitization may be induced despite the presence of a potent topical steroid.Source:
Ronald N. Shore, MD; Walter B. Shelley, MD, PhD. Arch Dermatol. 1974;109(3):397-399. doi:10.1001/archderm.1974.01630030055015.http://archderm.jamanetwork.com/article.aspx?articleid=533859

Tempering influence on oxygen and water vapor transmission through a stearyl alcohol film
Abstract
Stearyl alcohol was layered on a filter paper support and tested for resistance to O2 and water vapor transmission following tempering. Tempering at 48C for 14 or 35 days caused the resistance to O2and water vapor transmission to increase. The resistance to O2 and water vapor transport was increased 80% and 50% respectively, after 35 days. Likely mechanistic explanations include the healing of crystal imperfections and the development of a more extensive and better linked arrangement of lipid crystalline platelets.Source:
J. J. Kester, O. Fennema. Journal of the American Oil Chemists’ Society. August 1989, Volume 66, Issue 8, pp 1154-1157.http://link.springer.com/article/10.1007/BF02670102

Phase diagram of mixtures of stearic acid and stearyl alcohol
Abstract
Stearyl alcohol (98.4%), stearic acid (96.0%) and their binary mixtures were investigated by differential scanning calorimetry (DSC) at a heating and cooling rate of 10 K min−1. The phase diagrams on heating and cooling were constructed and showed a eutectic behavior for the solid–liquid equilibrium line. In the heating phase diagram, the eutectic line was not always visible due to the existence of a phase transition in the solid state. A shift in the eutectic phase composition towards the acid was observed on cooling. The cooling and heating phase diagrams further differed in the fact that only two exotherms were observed during cooling where three endotherms were observed during heating. A plot of the enthalpy of the mixtures versus the mole fraction shows that different processes are involved in the solid state.Source:
François G Gandolfo, Arjen Bot, Eckhard Flöter. Thermochimica Acta. Volume 404, Issues 1–2, 4 September 2003, Pages 9–17. doi:10.1016/S0040-6031(03)00086-8http://www.sciencedirect.com/science/article/pii/S0040603103000868

Glyceryl Stearate

Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis
Background/aims: Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20% glycerine was compared with its placebo and with a medicinally authorised cream with 4% urea (combined with 4% sodium chloride) in the treatment of dry skin.
Conclusions: Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis.Source:
M. Lodén,A.-C. Andersson,C. Andersson,T. Frödin, H. Öman and M. Lindberg. Skin Research and Technology. Volume 7, Issue 4, pages 209–213, November 2001. DOI: 10.1034/j.1600-0846.2001.70401.xhttp://onlinelibrary.wiley.com/doi/10.1034/j.1600-0846.2001.70401.x/abstract

PEG-100 Stearate

PEG-100 Stearate is made by combining natural oils (oftentimes palm or coconut) with Stearic Acid to form a water-soluble ester. It can also be a synthetic polymer made by combining Oxirane (Ethylene Oxide) and fatty acids (source). PEG-100 Stearate is primarily used by the cosmetics and beauty care industry as an emollient, an emulsifier and a moisturizer, although PEG Stearates in general are also known to clean the skin and hair by helping water to mix with oil and dirt so that they can be rinsed away, according to CosmeticsInfo.org.

Unexpected skin barrier influence from nonionic emulsifiers
Abstract
Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.Source:
Ebba Bárány, Magnus Lindberg, Marie Lodén. International Journal of Pharmaceutics. Volume 195, Issues 1–2, 15 February 2000, Pages 189–195. doi:10.1016/S0378-5173(99)00388-9http://www.sciencedirect.com/science/article/pii/S0378517399003889

Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions
Abstract
Multiple W/O/W emulsions for topical application using Span 80 as a lipophilic emulsifier were prepared. Several hydrophilic emulsifiers were tested in respect of their suitability for the preparation of multiple emulsions. In addition, the effect of different oil-phase compositions on emulsion stability was investigated. The physicochemical parameters of the formulations were characterized and their long-term stability was evaluated by means of rheological measurements, droplet size observations and conductivity analysis.
As discovered, the modification of an oil-phase composition results in a decrease in the diffusion coefficient of water and water-soluble substances and, consequently, in enhanced stability. The influence of the release of electrolytes from the inner to the outer water phase on the emulsion stability behaviour was investigated. It was found, that the effect of the hydrophilic emulsifiers on the formulation properties is related not only to its HLB value, but rather to its chemical composition.
As a result, polyethoxylated ethers of fatty alcohols (C = 16–18) with HLBs between 15.3 and 16.2 appear to be the most suitable ones for creating stable formulations.Source:
T. Schmidts, , D. Dobler, C. Nissing, F. Runkel. Journal of Colloid and Interface Science. Volume 338, Issue 1, 1 October 2009, Pages 184–192. doi:10.1016/j.jcis.2009.06.033doi:10.1016/j.jcis.2009.06.033http://www.sciencedirect.com/science/article/pii/S0021979709007632

Exposure data for cosmetic products: lipstick, body lotion, and face cream
Abstract
Accurate exposure information for cosmetic products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of cosmetic product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. The study included three widely used cosmetic product types: lipstick, body lotion, and face cream. Three hundred and sixty women, ages 19–65 years, who regularly use the products of interest, were recruited at ten different geographical locations within the US. The number of recruits was chosen to ensure a minimum of 300 completes per product type. Subjects were provided with prototype test products, and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analysis of the data was conducted to derive summary distribution of use patterns. The mean and median usage per application, respectively, for the three products was: face cream, 1.22 g and 0.84 g; lipstick, 10 mg and 5 mg; and body lotion, 4.42 g and 3.45 g. The mean and median usage per day for the three products was: face cream, 2.05 g and 1.53 g; lipstick, 24 mg and 13 mg; and body lotion, 8.70 g and 7.63 g. The mean number of applications per day for face cream and lipstick was 1.77 and 2.35, respectively. For body lotion, the mean number of applications per day was dependent on body area, and was 2.12, 1.52, 1.11, 0.95, 0.43, 0.26, and 0.40 for hands, arms, legs, feet, neck and throat, back, and other body areas, respectively. The effect of product preference on use practices was also investigated. This study provides current cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.Source:
L.J. Loretz, A.M. Api, L.M. Barraj, J. Burdick, W.E. Dressler, S.D. Gettings, H. Han Hsu, Y.H.L. Pan, T.A. Re, K.J. Renskers, A. Rothenstein, C.G. Scrafford, C. Sewall. Food and Chemical Toxicology. Volume 43, Issue 2, February 2005, Pages 279–291. doi:10.1016/j.fct.2004.09.016http://www.sciencedirect.com/science/article/pii/S0278691504003138 /

Selective hydrogenolysis of glycerol to propylene glycol on Cu–ZnO catalysts
Abstract
Hydrogenolysis of biomass-derived glycerol is an alternative route to sustainable production of propylene glycol. Cu–ZnO catalysts were prepared by coprecipitation with a range of Cu/Zn atomic ratio (0.6–2.0) and examined in glycerol hydrogenolysis to propylene glycol at 453–513 K and 4.2 MPa H2. These catalysts possess acid and hydrogenation sites required for bifunctional glycerol reaction pathways, most likely involving glycerol dehydration to acetol and glycidol intermediates on acidic ZnO surfaces, and their subsequent hydrogenation on Cu surfaces. Glycerol hydrogenolysis conversions and selectivities depend on Cu and ZnO particle sizes. Smaller ZnO and Cu domains led to higher conversions and propylene glycol selectivities, respectively. A high propylene glycol selectivity (83.6%), with a 94.3% combined selectivity to propylene glycol and ethylene glycol (also a valuable product) was achieved at 22.5% glycerol conversion at 473 K on Cu–ZnO (Cu/Zn = 1.0) with relatively small Cu particles. Reaction temperature effects showed that optimal temperatures (e.g. 493 K) are required for high propylene glycol selectivities, probably as a result of optimized adsorption and transformation of the reaction intermediates on the catalyst surfaces. These preliminary results provide guidance for the synthesis of more efficient Cu–ZnO catalysts and for the optimization of reaction parameters for selective glycerol hydrogenolysis to produce propylene glycol.Source:
Shuai Wang, Haichao Liu. Catalysis Letters. August 2007, Volume 117, Issue 1-2, pp 62-67.http://link.springer.com/article/10.1007/s10562-007-9106-9

Low-pressure hydrogenolysis of glycerol to propylene glycol
Abstract
Hydrogenolysis of glycerol to propylene glycol was performed using nickel, palladium, platinum, copper, and copper-chromite catalysts. The effects of temperature, hydrogen pressure, initial water content, choice of catalyst, catalyst reduction temperature, and the amount of catalyst were evaluated. At temperatures above 200 °C and hydrogen pressure of 200 psi, the selectivity to propylene glycol decreased due to excessive hydrogenolysis of the propylene glycol. At 200 psi and 200 °C the pressures and temperaures were significantly lower than those reported in the literature while maintaining high selectivities and good conversions. The yield of propylene glycol increased with decreasing water content. A new reaction pathway for converting glycerol to propylene glycol via an intermediate was validated by isolating the acetol intermediate.Source:
Mohanprasad A. Dasari,Pim-Pahn Kiatsimkul,Willam R. Sutterlin, Galen J. Suppes. Applied Catalysis A: General
Volume 281, Issues 1–2, 18 March 2005, Pages 225–231. doi:10.1016/j.apcata.2004.11.033http://www.sciencedirect.com/science/article/pii/S0926860X0400941X

Hydrolyzed Collagen

Hyrdrolyzed Collagen is a processed form of Collagen that is obtained by breaking down Collagen fibers utilizing heat or caustic solutions. It contains 20 different amino acids, including 8 of the 9 essential amino acids. Essential amino acids cannot be created the human body, which means that the only way our bodies can acquire them is through ingestion.Source:http://www.essen-nutrition.com/blog/entry/hydrolyzed-collagen-health-benefits

Contact Dermatitis to Botanical Extracts.
Abstract
A review of the literature of reported cases of contact dermatitis to a variety of natural herbal extracts is presented. Natural extracts are commonly used ingredients in many cosmetic preparations and homeopathic remedies. Although the term natural botanical extracts inherently purports to have beneficial and benign properties, these extracts can cause adverse reactions in individuals. As such, dermatologists should be cognizant of these agents as possible sources of allergenicity in patients presenting with contact dermatitis.Source:
Kiken, David A.; Cohen, David E. American Journal of Contact Dermatitis:Official Journal of The American Contact Dermatitis Society:September 2002http://journals.lww.com/dermatitis/Abstract/2002/09000/Contact_Dermatitis_to_Botanical_Extracts.10.aspx

Conversion of α-amyrin into centellosides by plant cell cultures of Centella asiatica
Abstract
Plant cell cultures of Centella asiatica produce small quantities of centellosides: madecassosid > asiaticosid > madecassic acid > asiatic acid. To obtain a more efficient production system of these bioactive triterpenoid compounds, we developed a process where the substrate, α-amyrin, was converted into centellosides by cell suspensions of C. asiatica. When α-amyrin in acetone was added at 0.01 mg/ml−1 to the culture medium, together with the permeabilizing agent DMSO, after 7 days nearly 50% had penetrated the plant cells, of which almost 84% was transformed into centellosides. The system therefore efficiently converts α-amyrin into centellosides, thus opening a new possibility for the production of these compounds.Source:
Liliana Hernandez-Vazquez, Mercedes Bonfill, Elisabeth Moyano, Rosa M. Cusido, Arturo Navarro-Ocaña, Javier Palazon. Biotechnology Letters. February 2010, Volume 32, Issue 2, pp 315-319.http://link.springer.com/article/10.1007/s10529-009-0143-x

Capsicum

Green synthesis of silver nanoparticles using Capsicum annuum L. extract
Abstract
Silver nanoparticles (NPs) were rapidly synthesized by treating silver ions with a Capsicum annuum L. extract. The reaction process was simple and convenient to handle, and was monitored using ultraviolet-visible spectroscopy (UV-vis). The effect of Capsicum annuum L.proteins on the formation of silver NPs was investigated using X-ray photoemission spectroscopy (XPS), electrochemical measurements, Fourier-transform infrared spectroscopy(FTIR) and differential spectrum techniques. The morphology and crystalline phase of the NPs were determined from transmission electron microscopy (TEM), selected area electron diffraction (SAED) and X-ray diffraction (XRD) spectra. The results indicated that the proteins, which have amine groups, played a reducing and controlling role during the formation of silver NPs in the solutions, and that the secondary structure of the proteins changed after reaction withsilver ions. The crystalline phase of the NPs changed from polycrystalline to single crystalline and increased in size with increasing reaction time. A recognition–reduction–limited nucleation and growth model was suggested to explain the possible formation mechanism of silver NPs inCapsicum annuum L. extract.Source:Shikuo Li,Yuhua Shen,Anjian Xie,Xuerong Yu,Lingguang Qiu,Li Zhang and Qingfeng Zhang.. Green Chem., 2007,9, 852-858. DOI: 10.1039/B615357Ghttp://pubs.rsc.org/en/content/articlelanding/2007/gc/b615357g#!divAbstract

Changes in Phytochemical and Antioxidant Activity of Selected Pepper Cultivars (Capsicum Species) As Influenced by Maturity
The effect of fruit maturation on changes in carotenoids, flavonoids, total soluble reducing equivalents, phenolic acids, ascorbic acid, and antioxidant activity (AOX) in different pepper types (Capsicum annuum, Capsicum frutescens, and Capsicum chinese) was determined. Generally, the concentration of these chemical constituents increased as the peppers reached maturity. Peppers contained high levels of l-ascorbic acid and carotenoids at maturity, contributing 124−338% of the RDA for vitamin C and 0.33−336 RE/100 g of provitamin A activity, respectively. Levels of phenolic acids, capxanthin, and zeaxanthin generally increased during maturation, whereas the level of lutein declined. Flavonoid concentrations varied greatly among the pepper types analyzed and were negatively correlated to AOX under the conditions of the β-carotene−linoleic assay. Model systems were used to aid in understanding the relationship between flavonoids and AOX. Significant increases in AOX were observed in pepper juice models in response to increasing dilution factors and the presence of EDTA, indicating a pro-oxidant effect due to metal ions in the system. In vitro models demonstrated that increasing levels of flavonoids in combination with constant levels of caffeic and ascorbic acid gave a resultant AOX that was either additive of the two compounds or competitive in their ability to scavenge peroxyl radicals. The model systems were in good agreement with the chemical composition of the pepper cultivars and reflected the interactions affecting AOX. More research is needed to understand the complex interactions that occur among various antioxidants present in pepper extracts.Source:
L. R. Howard , S. T. Talcott , C. H. Brenes , and B. Villalon . J. Agric. Food Chem., 2000, 48 (5), pp 1713–1720. DOI: 10.1021/jf990916thttp://pubs.acs.org/doi/abs/10.1021/jf990916t

The antimicrobial properties of chile peppers (Capsicumspecies) and their uses in Mayan medicine
Abstract
A survey of the Mayan pharmacopoeia revealed that tissues of Capsicum species (Solanaceae) are included in a number of herbal remedies for a variety of ailments of probable microbial origin. Using a filter disk assay, plain and heated aqueous extracts from fresh Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens varieties were tested for their antimicrobial effects with fifteen bacterial species and one yeast species. Two pungent compounds found inCapsicum species (capsaicin and dihydrocapsaicin) were also tested for their antimicrobial effects. The plain and heated extracts were found to exhibit varying degrees of inhibition against Bacillus cereus, Bacillus subtilis, Clostridium sporogenes, Clostridium tetani, and Streptococcus pyogenes.Source:
Robert H. Cichewicz, Patrick A. Thorpe. Journal of EthnopharmacologyVolume 52, Issue 2, June 1996, Pages 61–70. doi:10.1016/0378-8741(96)01384-0http://www.sciencedirect.com/science/article/pii/0378874196013840

Carbomer

The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro
Abstract
Two mucoadhesive polymers, chitosan-glutamate and carbomer, were studied in an in vitro model (Caco-2 cell monolayers) with respect to their ability to enhance intestinal peptide drug delivery. Preparations of the polymers at concentrations of 0.5, 1.0, and 1.5% w/v (chitosan), and of 0.5 and 1.0% w/v (carbomer) were applied to the apical side of Caco-2 cell monolayers. The effects on transepithelial electrical resistance (TEER), paracellular transport of a FITC-dextran of a molecular weight of 4400 (FD-4) and [14C]mannitol were measured. Paracellular transport of FD-4 was visualized by means of confocal laser scanning microscopy (CLSM). Furthermore, the impact of lowering the pH of the polymer solutions to pH 4 on the integrity of the cell layer was determined. The results show that both polymers were able to decrease TEER of Caco-2 cell layers significantly. In the case of carbomer, CLSM revealed a partial opening of epithelial tight junctions. Lowering of the pH in the control and polymer solutions to pH 4 resulted in every case in the irreversible damage of a large percentage of the cells, as shown by CLSM. Transport studies with [14C]mannitol and FD-4 showed only during co-application of carbomer significantly increased fluxes, whereas no difference from the control solution could be detected for chitosan-glutamate. A threshold value of about 50% of TEER reduction has been identified, which allows for transport of hydrophilic compounds across the cell monolayers of the Caco-2 cell model.Source:
Gerrit Borchard, Henrik L. Lueβen, Albertus G. de Boer, J.Coos Verhoef, Claus-M. Lehr, Hans E. Junginger. Journal of Controlled Release Volume 39, Issues 2–3, May 1996, Pages 131–138. doi:10.1016/0168-3659(95)00146-8http://www.sciencedirect.com/science/article/pii/0168365995001468

Cytoprotective effects of Hyaluronic Acid and Carbomer 934P in Ocular Surface Epithelial Cells
Abstract:
To investigate in vitro the cell toxicity and antioxidant effects of two major tear substitutes, hyaluronic acid and a widely used carbomer, with and without preservative.
Chang conjunctival cells were treated with different concentrations of unpreserved or preserved carbomer 934P (0.03% and 0.3%), unpreserved or preserved hyaluronic acid (0.018% and 0.18%), and benzalkonium chloride (BAC 0.0005% and 0.005%) for 15 minutes or for 15 minutes with 24 hours of cell recovery, according to previously validated methods. Microplate cold light cytofluorometry was performed to evaluate cell viability (neutral red test), chromatin condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests). Confocal microscopy was used to explore morphologic changes.
No alterations were found with unpreserved and preserved hyaluronic acid at all concentrations and times tested. A decrease in cell viability with chromatin condensation appeared with 0.3% preserved carbomer 934P at the two times tested. This cytotoxicity, however, was significantly less than that observed with BAC alone, although the same concentrations of preservative were used. Unpreserved carbomer 934P induced no modification of cell viability after 15 minutes but a significant decrease in chromatin condensation, reversible after 24 hours of cell recovery, when a delayed decrease in cell viability was observed. Production of reactive oxygen species (ROS) decreased with the four formulations of tear substitutes tested at their usual concentrations, whereas a significant production of ROS occurred with BAC.
These two ophthalmic hydrogels have no cytotoxicity but possess antioxidant properties and tend to reduce the toxic effects of preservatives. These results may allow use of hydrogels, not only in dry eye but also in ocular surface disorders involving oxidative stress and in ophthalmic drug therapy to improve ocular tolerance.Source:
Cellular Pharmacotoxicology Unit, Toxicology Laboratory, Quinze-Vingts, National Hospital Center for Ophthalmology, Ambroise Paré AP-HP, University of Paris-V, Paris, France.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.66). 12/2002; 43(11):3409-15.

Temoporfin-loaded liposomal gels: Viscoelastic properties and in vitro skin penetration
Abstract
Temoporfin (mTHPC) is a potent second-generation photosensitizer. The primary object of this study was to develop a topical mTHPC-loaded liposomal hydrogel able to deliver mTHPC into the stratum corneum (SC) and deeper skin layers. This study was conducted (1) to determine the effect of carbomer concentration, used as a gelling agent, and the effect of phosphatidylcholine (PC) content of lecithin, used for the liposome preparation, on viscoelastic properties and viscosity of liposomal gels and (2) to determine the relationship between rheological properties of gels and the skin penetration of mTHPC. Liposomal hydrogels revealed plastic flow behaviour. The increase of carbomer concentration induced a domination of elastic over viscous behaviour of gels. There was an inverse relationship between the elasticity of gels and mTHPC-penetration. Viscosity also increased with the increment of carbomer concentration, reducing the mTHPC-penetration. Liposomal gels containing lecithin of smaller PC-content (i.e. smaller purity) exhibited a more elastic solid behaviour than gels containing lecithin with high PC-content, and showed smaller mTHPC-penetration. The gel containing 0.75%, w/w, carbomer and lecithin with high PC-content was considered to be the optimal formulation, since it delivered high amounts of mTHPC to the SC and deeper skin layers, and it possessed desirable rheological properties.Source:
Temoporfin-loaded liposomal gels: Viscoelastic properties andin vitro skin penetration. Nina Dragicevic-Curic, Sven Winter, Mirjana Stupar, Jela Milic, Danina Krajišnik, Burkhard Gitter, Alfred Fahr. International Journal of Pharmaceutics. Volume 373, Issues 1–2, 21 May 2009, Pages 77–84

Xanthan gum biosynthesis and application: a biochemical /genetic perspective
Abstract:
Xanthan gum is a complex exopolysaccharide produced by the plant-pathogenic bacteriumXanthomonas campestris pv. campestris. It consists of D-glucosyl, D-mannosyl, and D-glucuronyl acid residues in a molar ratio of 2:2:1 and variable proportions of O-acetyl and pyruvyl residues. Because of its physical properties, it is widely used as a thickener or viscosifier in both food and non-food industries. Xanthan gum is also used as a stabilizer for a wide variety of suspensions, emulsions, and foams. This article outlines aspects of the biochemical assembly and genetic loci involved in its biosynthesis, including the synthesis of the sugar nucleotide substrates, the building and decoration of the pentasaccharide subunit, and the polymerization and secretion of the polymer. An overview of the applications and industrial production of xanthan is also covered.Source:
Xanthan gum biosynthesis and application: a biochemical /genetic perspective. A. Becker,F. Katzen, A. Pühler, L. Ielpi. Applied Microbiology and Biotechnology. August 1998, Volume 50, Issue 2, pp 145-152.http://link.springer.com/article/10.1007/s002530051269

Intermolecular binding of xanthan gum and carob gum
Abstract.
Gels are a representative state for polysaccharides in both natural and artificial systems. The nature of the inter-chain associations within the junction zones is important and models for such interactions between like polysaccharides are based on X-ray diffraction studies of oriented gels. Here we describe the extension of such studies to a binary gel (xanthan-carob) in order to characterize for the first time intermolecular binding between different polysaccharides. Xanthan-carob binding has been proposed to explain gelation of the mixtures and as a model for host-pathogen recognition and adhesion of Xanthomonas bacteria within plant vascular systems. Our data suggest that the established model1–7 is incorrect and point to an alternative association mechanism.

Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour..
Abstract:
A comparative investigation has been undertaken to assess the performance of xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) as hydrophilic matrix-forming agents in respect of compaction characteristics and in vitro drug release behaviour. The overall compaction characteristics are found to be quite similar to each other and typical of polymer behaviour. But the flow characteristics are different, i.e., XG is more readily flowable than HPMC. The observed difference in drug release profiles between these two potential excipients are explored and explained by the difference in their hydrophilicity and subsequent hydration properties.Source:
Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour. Mohammad Mahiuddin Talukdar, Armand Michoel, Patrick Rombaut, Renaat Kinget. International Journal of Pharmaceutics.Volume 129, Issues 1–2, 8 March 1996, Pages 233–241. doi:10.1016/0378-5173(95)04355-1

Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography
Abstract
A reversed-phased HPLC method that allows the separation and simultaneous determination of the preservatives benzoic (BA) and sorbic acids (SA), methyl- (MP) and propylparabens (PP) is described. The separations were effected by using an initial mobile phase of methanol–acetate buffer (pH 4.4) (35:65) to elute BA, SA and MP and changing the mobile phase composition to methanol–acetate buffer (pH 4.4) (50:50) thereafter. The detector wavelength was set at 254 nm. Under these conditions, separation of the four components was achieved in less than 23 min. Analytical characteristics of the separation such as limit of detection, limit of quantification, linear range and reproducibility were evaluated. The developed method was applied to the determination of 67 foodstuffs (mainly imported), comprising soft drinks, jams, sauces, canned fruits/vegetables, dried vegetables/fruits and others. The range of preservatives found were from not detected (nd)—1260, nd—1390, nd—44.8 and nd—221 mg kg−1 for BA, SA, MP and PP, respectively.
Simultaneous determination of preservatives (benzoic acid, sorbic acid, methylparaben and propylparaben) in foodstuffs using high-performance liquid chromatography.Source:
Bahruddin Saad,Md. Fazlul Bari, Muhammad Idiris Saleh, Kamarudzaman Ahmad, Mohd. Khairuddin Mohd. Talib. Journal of Chromatography A. Volume 1073, Issues 1–2, 6 May 2005, Pages 393–397. 28th International Symposium on High Performance Liquid Phase Separations and Related Techniques. HPLC 2004. doi:10.1016/j.chroma.2004.10.105

3 Final Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, and Butylparaben
Abstract:
The Parabens are esters of p-hydroxybenzoic acid (PHBA) and are the most commonly used as preservatives in cosmetic formulations. Data obtained from chronic administration studies indicate that Parabens are rapidly absorbed, metabolized, and excreted.
Acute chronic and subchronic toxicity studies in animals indicate that Parabens are practically nontoxic by various routes of administration. Methylparaben and Ethylparaben at 100 percent concentration were slightly irritating when instilled into the eyes of rabbits.
Numerous in vitro mutagenicity studies indicate that the Parabens are non-mutagenic. Methylparaben was noncarcinogenic when injected in rodents or when administered intravaginally in rats. Cocarcinogenesis studies on Propyl- and Methylparaben were negative. Teratogenic studies on Methyl- and Ethylparaben were also negative.
Parabens are practically nonirritating and nonsensitizing in the human population with normal skin. Paraben sensitization has been reported when Paraben-containing medicaments have been applied to damaged or broken skin. Photo-contact sensitization and phototoxicity tests on product formations of Methyl-, Propyl-, and/or Butylparaben gave no evidence of significant photoreactivity.
It is concluded that Methylparaben, Ethylparaben, Propylparaben, and Butylparaben are safe as cosmetic ingredients in the present practices of use.Source:
3 Final Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, and Butylparaben. . International Journal of ToxicologySeptember/October 1984 vol. 3 no. 5147-209. doi: 10.3109/10915818409021274

Methylparaben potentiates UV-induced damage of skin keratinocytes.
Abstract:
For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24 h, exposed to UVB (15 or 30 mJ/cm2) and further cultured for another 24 h. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. Oxidative stress, nitric oxide (NO) production and cellular lipid peroxidation were measured using fluorescent probes. In addition, activation of nuclear factor kappa B and activator protein-1 was assessed by electro-mobility gel-shift assay. Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, NO production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.Source:
Methylparaben potentiates UV-induced damage of skin keratinocytes. Osamu Handa, Satoshi Kokura, Satoko Adachi, Tomohisa Takagi, Yuji Naito, Toru Tanigawa, Norimasa Yoshida,Toshikazu Yoshikawa.Toxicology. Volume 227, Issues 1–2, 3 October 2006, Pages 62–72. doi:10.1016/j.tox.2006.07.018

Propyl Paraben

Skin Permeation of Parabens in Excised Guinea Pig Dorsal Skin, Its Modification by Penetration Enhancers and Their Relationship with n-Octanol/Water Partition Coefficients
Abstract
Skin penetration of methyl, ethyl, propyl and butyl parabens through excised guinea pig dorsal skin was examined, and effects of the penetration enhancers, l-menthol plus ethanol, ethanol itself and N-dodecyl-2-pyrrolidone, were observed. Permeability coefficients of the parabens correlated with n-octanol/water partition coefficients. Addition of 1% l-menthol in 15% ethanol about sixteen times increased the permeability coefficient of methyl paraben, whereas this enhancer decreased that of butyl paraben to about one fifth of the control value. A similar, though weaker, tendency was observed for the effects of 15% ethanol itself. 0.025% suspension of N-dodecyl-2-pyrrolidone increased the permeability coefficient of methyl paraben about seven times, whereas it did not change that of butyl paraben significantly. Therefore, dependency of the permeability coefficients of the parabens on n-octanol/water partition coefficients almost disappeared in the presence of this compound. A spin label study with stratum corneum lipid liposomes revealed that increase of fluidity of the lipid bilayer by these penetration enhancers corresponded with their enhancement effects on skin penetration of methyl paraben. Perturbation of stratum corneum lipid lamella thus seems to be related with their enhancement of the absorption of the hydrophiic paraben.Source:
Shuji KITAGAWA, Hui LI, Shinji SATO. Chemical and Pharmaceutical Bulletin. Vol. 45 (1997) No. 8 P 1354-1357. http://doi.org/10.1248/cpb.45.1354https://www.jstage.jst.go.jp/article/cpb1958/45/8/45_8_1354/_article

RELEASE OF PROPYL PARABEN FROM A POLYMER COATING INTO WATER AND FOOD SIMULATING SOLVENTS FOR ANTIMICROBIAL PACKAGING APPLICATIONS.
Abstract:
The release phenomena of propyl paraben from a polymer coating to water and three food simulating solvents (10% aqueous ethanol, 50% aqueous ethanol, n-heptane) were studied for antimicrobial packaging applications. The effects of food simulating solvent, initial concentration in the coating and temperature on the propyl paraben release were examined. The initial concentration of propyl paraben in the coating ranged from 1.26 × 104 to 10.52 × 104 g/m3 and the temperature from 5.5 to 30C. For water, the release was controlled by Fickian diffusion with constant diffusion coefficient (7±11 × 10-11 cm2/s at 30C), and independent of the initial concentration. For 10% ethanol, the release followed again the Fickian model with constant diffusion coefficient (30±40 × 10-11 cm2/s at 30C). For 50% ethanol and n-heptane, the release was instantaneous and not controlled by Fickian diffusion. For the release into water, the activation energy for diffusion from the Arrhenius relationship was around 88 kJ/mole.Source:
RELEASE OF PROPYL PARABEN FROM A POLYMER COATING INTO WATER AND FOOD SIMULATING SOLVENTS FOR ANTIMICROBIAL PACKAGING APPLICATIONS. DONGHWAN CHUNG, SPYRIDON E. PAPADAKIS and KIT L. YAM. Journal of Food Processing and Preservation. Volume 25, Issue 1, pages 71–87, April 2001. DOI: 10.1111/j.1745-4549.2001.tb00444.x

Safety assessment of propyl paraben: a review of the published literature.
Abstract
Propyl paraben (CAS no. 94-13-3) is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. It is an ester of p-hydroxybenzoate. Propyl paraben is readily absorbed via the gastrointestinal tract and dermis. It is hydrolyzed to p-hydroxybenzoic acid, conjugated and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that propyl paraben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-effect levels (NOEL) as high as 1200–4000 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5500 mg/kg is posited. Propyl paraben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5–15% in patch testing are needed to elicit reaction in susceptible individuals. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.Source:
Safety assessment of propyl paraben: a review of the published literature M.G. Soni, G.A. Burdock,S.L. Taylor,N.A. Greenberg. Food and Chemical Toxicology. Volume 39, Issue 6, June 2001, Pages 513–532. doi:10.1016/S0278-6915(00)00162-9

Jojoba Oil

Jojoba oil wax esters and derived fatty acids and alcohols: Gas chromatographic analyses
Abstract
HCl-catalyzed ethanolysis followed by saponification readily surmounts the resistance of long chain wax esters to direct hydrolysis by alkali. Additionally, choosing ethyl instead of methyl esters allows baseline separations between long-chain alcohols and corresponding esters in gas liquid chromatographic (GLC) analysis of total alcohol and acid components before saponification. Liquid wax esters were analyzed on a temperature-programmed 3% OV-1 silicone column. Geographical and genetic effects on the variability of jojoba oil composition were investigated with five different seed samples. Major constituents in jojoba seed oil from shrubs in the Arizona deserts, as indicated by GLC analyses of oil, ethanolysis product, isolated fatty alcohols and methyl esters of isolated fatty acids, were C40 wax ester 30%, C42 wax ester 50% and C44 wax ester 10%; octadecenoic acid 6%; eicosenoic acid 35%, docosenoic acid 7%, eicosenol 22%, docosenol 21% and tetracosenol 4%. Oil from smaller leaved prostrate plants growing along California’s oceanside showed a slight tendency toward higher molecular size than oils from the California desert and Arizona specimens. The wax esters are made up of a dispro-portionately large amount of docosenyl eicosenoate and are not a random combination of constituent acids and alcohols.Lunaria annua synthetic wax ester oil was used as a model for evaluating the analytical procedures.Source:Thomas K. Miwa, Journal of the American Oil Chemists Society June 1971, Volume 48, Issue 6, pp 259-264. DOI 10.1007/BF02638458http://link.springer.com/article/10.1007/BF02638458

Skin nonpenetrating sunscreens for cosmetic and pharmaceutical formulations.
Abstract:
Ultraviolet (UV) solar radiation produces harmful effects on the skin including sunburn, local immunosuppression, skin photoaging, and cutaneous malignancies. Although application of sunscreens is the “gold standard” for protecting the skin from UV radiation, studies have shown that currently used sunscreens can cause adverse skin and systemic reactions, owing to their penetration into the viable cutaneous strata and to transdermal absorption. This paper presents new nonpermeating sunscreens (NPSUN) suitable for use in cosmetic and pharmaceutical products. The basic idea behind the design of the new photoprotectors was to immobilize UV-absorbing moieties in the Jojoba oil chemical backbone. The physicochemical characteristics of NPSUNs allow these derivatives to remain confined to the upper stratum corneum where the sunscreen molecule acts, with no further clearance to deeper dermal strata or systemic circulation. As an example, no permeation across the skin of methoxycinnamate-NPSUN was observed during 24-hour in vitro experiments, after topical application of either unformulated substances or of methoxycinnamate-NPSUNs formulated in oil-in-water cream, in water-in-oil cream, or in Jojoba oil. Another approach to increase the photoprotective effect against the UV radiation is targeting the delivery of α tocoperol into the deeper skin layers and across the cell membranes. This is necessary for optimal photoprotection and prevention of malignant processes. For this purpose, ethosomal vitamin E compositions were designed, characterized, and tested. Efficient intracellular and dermal accumulation of vitamin E from ethosomes was demonstrated.Source:
Skin nonpenetrating sunscreens for cosmetic and pharmaceutical formulations Elka Touitou, PhD, Biana Godin, PhD. Clinics in Dermatology. Volume 26, Issue 4, July–August 2008, Pages 375–379. doi:10.1016/j.clindermatol.2008.01.014

Solubilization of lycopene in jojoba oil microemulsion.
Abstract
The unique properties of jojoba oil make it an essential raw material in the manufacture of cosmetics. New, totally dilutable U-type microemulsions of water, jojoba oil, alcohols, and the nonionic surfactant polyoxyethylene-10EO-oleyl alcohol (Brij 96V) have been formulated recently. Here, these microemulsions are shown to be capable of solubilizing lycopene, a nutraceutical insoluble in water and/or oil, much more effectively than the solvent (or a solvent and surfactant blend) can dissolve them. In water-in-oil (W/O) and oil-in-water (O/W) microemulsions with 10 and 90 wt% water, respectively, the normalized maximal solubilization efficiency α is ca. 20-fold larger than its solubility. The solubilization capacity of the system is mainly surfactant-concentration dependent. The lycopene resides at the interfaces of the W/O and O/W microemulsions and engenders significant structural changes in the organization of the microemulsion droplets. In the absence of lycopene, the droplets are spherical; when lycopene is added, compaction of the droplets and formation of threadlike droplets are observed. On further addition of lycopene, the bridging effect wanes and the droplets revert to a spherical shape. The enhanced solubilization demonstrated for lycopene opens up new options for formulators interested in making liquid and transparent products for cosmetic or pharmaceutical uses..

Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation.
Abstract
Orange peel oil has previously been shown to be a promoter of mouse skin tumors. It has been assumed that this activity is due to its major (95%) constituent, d-limonene. We have tested both orange peel oil and purified d-limonene as skin tumor promoters in a two-stage skin carcinogenesis model in which tumors were initiated with 7, 12-dimethylbenz[a]-anthracene. We confirmed that topically applied orange peel oil is a very weak promoter of both skin papillomas and carcinomas. However, this promotional activity could not be accounted for by topically applied d-limonene. We thus feel that one or more minor components of orange peel oil has promotional activity. Neither orange peel oil nor d-limonene had promotional activity when given via the diet.Source:
Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation. J.Abiodun Elegbede, Terese H. Maltzman, Ajit K. Verma, Martin A. Tanner, Charles E. Elson and Michael N. Gould, Carcinogenesis (1986) 7 (12):2047-2049. doi: 10.1093/carcin/7.12.2047

Citrus Peel Use Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Skin.
Abstract:
Limonene has demonstrated efficacy in preclinical models of breast and colon cancers. The principal sources of d-limonene are the oils of orange, grapefruit, and lemon. The present case-control study was designed to determine the usual citrus consumption patterns of an older Southwestern population and to then evaluate how this citrus consumption varied with history of squamous cell carcinoma (SCC) of the skin. In this Arizona population, 64.3% and 74.5% of the respondents reported weekly consumption of citrus fruits and citrus juices, respectively. Orange juice (78.5%), orange (74.3%), and grapefruit (65.3%) were the predominant varieties of citrus consumed. Peel consumption was not uncommon, with 34.7% of all subjects reporting citrus peel use. We found no association between the overall consumption of citrus fruits [odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.73-1.32] or citrus juices (OR = 0.97, 95% CI = 0.71-1.31) and skin SCC. However, the most striking feature was the protection purported by citrus peel consumption (OR = 0.66, 95% CI = 0.45-0.95). Moreover, there was a dose-response relationship between higher citrus peel in the diet and degree of risk lowering. This is the first study to explore the relationship between citrus peel consumption and human cancers. Our results show that peel consumption, the major source of dietary d-limonene, is not uncommon and may have a potential protective effect in relation to skin SCC. Further studies with large sample sizes are needed to more completely evaluate the interrelationships between peel intake, bioavailability of d-limonene, and other lifestyle factors.Source:
Citrus Peel Use Is Associated With Reduced Risk of Squamous Cell Carcinoma of the Skin. Iman A. Hakim, Robin B. Harris & Cheryl Ritenbaugh. Nutrition and Cancer. Volume 37, Issue 2, 2000. pages 161-168. DOI: 10.1207/S15327914NC372_7

Lemon Oil

Oxidized citrus oil (R-limonene): A frequent skin sensitizer in Europe
Background: Peel oil from citrus fruits consists of R-(+)-limonene, which is one of the most commonly used fragrance materials in technical products and in fine fragrances. This substance forms allergenic oxidation products during handling and storage.Objective: We wanted to study the frequency of allergic reactions to oxidized R-(+)-limonene in patients with dermatitis and find a suitable test preparation. Method: Patch testing with oxidized R-(+)-limonene was performed on 2273 patients at 4 dermatology clinics in Europe. Results: Of the consecutive patients tested, 3.8% to 3.9% had positive reactions in two of the clinics; 6.5% had positive reactions in the third clinic; and 0.3% had positive reactions in the fourth clinic. A total of 63 patients showed positive reactions. In total, 57% of the patients did not react to fragrance mix or balsam of Peru. We recommend testing with 3% oxidized R-(+)-limonene in patients referred for patch testing. Conclusion: The high frequency of oxidized limonene allergy provides clinical evidence for the European classification of R-(+)-limonene that contains oxidation products as skin sensitizers. (J Am Acad Dermatol 2002;47:709-14.)Source:
Mihály Matura, MD, PhDa, An Goossens, RPharm, PhDb, Olivia Bordalo, MDc,Begoña Garcia-Bravo, MDd, Kerstin Magnussona Karin Wrangsjö, MD, PhDe, Ann-Therese Karlberg, RPharm, PhDa. Journal of the American Academy of Dermatology. Volume 47, Issue 5, November 2002, Pages 709–714. doi:10.1067/mjd.2002.124817http://www.sciencedirect.com/science/article/pii/S0190962202001500

A study of the phototoxicity of lemon oil
Summary
Lemon oil contains furocoumarin derivatives and is known to cause phototoxicity. In this study, lemon oil was fractionated, and its phototoxic activity was measured by means of a biological assay. The substances producing phototoxicity were identified by high-performance liquid chromatography as being oxypeucedanin and bergapten. The phototoxic potency of oxypeucedanin was only one-quarter of that of bergapten. However, the amounts of these two phototoxic compounds present in lemon oils produced in different regions of the world varied by a factor of more than 20 (bergapten, 4–87 ppm; oxypeucedanin, 26–728 ppm), and their ratio was not constant. The two compounds accounted for essentially all of the phototoxic activity of all lemon-oil samples. Among various other citrus-essential oils investigated, lime oil and bitter-orange oil also contained large amounts of oxypeucedanin. Oxypeucedanin was found to elicit photopigmentation on colored-guinea-pig skin without preceding visible erythema.Source:
A study of the phototoxicity of lemon oil. M. Naganuma, S. Hirose, Y. Nakayama, K. Nakajima, T. Someya. Archives of Dermatological Research. October 1985, Volume 278, Issue 1, pp 31-36.http://link.springer.com/article/10.1007/BF00412492

Biochemical studies on a novel antioxidant from lemon oil and its biotechnological application in cosmetic dermatology.
Abstract
It is generally accepted that lipid peroxides play an important role in the pathogenesis of free radical-induced cellular injury and that antioxidants such as glutathione, ascorbic acid and alpha-tocopherolare vital in cellular defense against endogenous and exogenous oxidants. The purpose of this study was to investigate the effectiveness of a natural compound, derived from lemon oil extract, in controlling free radical-induced lipid peroxidation and tissue damage in the skin. We provide evidence that a compound isolated from lemon oil, which we have called Lem1, is endowed with a strongantioxidant activity and that it is capable of inhibiting free radical-mediated reactions, evaluated by both in vitro and in vivo biochemical systems. The present study aims to give a preclinical perspective on the biochemical properties of Lem1, a natural compound, as well as to provide a better understanding of the endogenous antioxidant potential of skin and the real validity of a natural antioxidant biotechnology in the antiaging management of the skin.Source:
Biochemical studies on a novel antioxidant from lemon oil and its biotechnological application in cosmetic dermatology. Calabrese V, Randazzo SD, Catalano C, Rizza V. Faculty of Medicine, Dept. of Chemistry, University of Catania, Italy. Calabrese@mbox.Unict.It. Drugs Under Experimental and Clinical Research [1999, 25(5):219-225]http://europepmc.org/abstract/med/10568210

Oxidative stress and antioxidants at skin biosurface: a novel antioxidant from lemon oil capable of inhibiting oxidative damage to the skin.
Abstract
Atmospheric pollutants are an important source of oxidative and nitrosative stress both to terrestrial plants and to animals. Skin, which has a highly differentiated and certainly complex organizational structure, is particularly vulnerable to free radical damage because of its contact with oxygen and with other environmental stimuli. Fruit and vegetables contain several classes of compounds that when ingested can potentially contribute to antioxidant defenses. In the present study we employed a novel gas chromatographic method to assess the antioxidant properties of a natural compound isolated fromlemon oil, which we have called Lem1. We provide experimental evidence that Lem1 is endowed with a strong antioxidant activity and that it is capable of inhibiting free radical-mediated reactions, as evaluated in vitro and in vivo. The present study extends our previous findings and demonstrates that topical application of Lem1 in healthy volunteers significantly increases the antioxidative potential of skin biosurface, thus highlighting the effectiveness of a natural antioxidant biotechnology in the antiaging management of skin.Source:
Calabrese V, Scapagnini G, Randazzo SD, Randazzo G, Catalano C, Geraci G, Morganti P. Faculty of Medicine, Department of Chemistry, University of Catania, Italy. Calabrese@mbox.Unict.it. Drugs Under Experimental and Clinical Research [1999, 25(6):281-287].http://europepmc.org/abstract/med/10713866

Grapefruit Oil

Oxidative stress and antioxidants at skin biosurface: a novel antioxidant from lemon oil capable of inhibiting oxidative damage to the skin.
Abstract
Atmospheric pollutants are an important source of oxidative and nitrosative stress both to terrestrial plants and to animals. Skin, which has a highly differentiated and certainly complex organizational structure, is particularly vulnerable to free radical damage because of its contact with oxygen and with other environmental stimuli. Fruit and vegetables contain several classes of compounds that when ingested can potentially contribute to antioxidant defenses. In the present study we employed a novel gas chromatographic method to assess the antioxidant properties of a natural compound isolated from lemon oil, which we have called Lem1. We provide experimental evidence that Lem1 is endowed with a strong antioxidant activity and that it is capable of inhibiting free radical-mediated reactions, as evaluated in vitro and in vivo. The present study extends our previous findings and demonstrates that topical application of Lem1 in healthy volunteers significantly increases the antioxidative potential of skin biosurface, thus highlighting the effectiveness of a natural antioxidant biotechnology in the antiaging management of skin.Source:Calabrese V,Scapagnini G,Randazzo SD,Randazzo G,Catalano C,Geraci G,Morganti PDrugs Under Experimental and Clinical Research [1999, 25(6):281-287]http://europepmc.org/abstract/med/10713866

Coumarins and psoralens in grapefruit peel oil.
Abstract
Four coumarins, four psoralens and two methoxyflavones were isolated and identified from the peel oil of grapefruit. Five of these compounds are reported as constituents of grapefruit oil for the first time, one of which, 5[(3,7-dimethyl-6-epoxy-2-octenyl) oxy]psoralen is a new natural product.Source:
Coumarins and psoralens in grapefruit peel oil. James H. Tatum, Robert E. Berry. Phytochemistry. Volume 18, Issue 3, 1979, Pages 500-502. doi:10.1016/S0031-9422(00)81903-2.

Hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat)
Abstract
Vitamin E acetate is often used rather than vitamin E as an ingredient of skin care products and dermatological preparations, because it lacks the free phenolic OH group. However, because of this the acetate as such is biologically inactive. In spite of this intrinsic inactivity, the skin is protected against the harmful effects of sunlight after topical application of vitamin E acetate. Therefore it is supposed that hydrolysis takes place in the skin and that the reaction product, the radical scavenger vitamin E, is responsible for the protection observed.
In this in vivo study with the rat, we have investigated the hydrolysis of RRR-α-tocopheryl acetate (vitamin E acetate) in the epidermis in relation to UV radiation protection. (As a measure of protection, we used the UV-induced binding of 8-methoxypsoralen to epidermal biomacromolecules.)
After a period of 5 h from a single application of vitamin E acetate, hydrolysis into free vitamin E was not observed. No protection was found at this time point, corresponding with the absence of vitamin E.
After treatment for 5 days, consisting of one topical application daily, the percentage of acetate present in the stratum corneum which was hydrolysed into free vitamin E was less than 1%, whereas the corresponding value for the viable layer of the epidermis was about 5%.
The hydrolysis of vitamin E acetate in the epidermis proceeded very slowly. As a result, the absolute amount of free vitamin E, found in the total epidermis after treatment for 5 days with the acetate, was only a few times higher than the normal level. Yet, this very small amount of free vitamin E proved to be sufficient for maximal protection in this animal model.
The results show that vitamin E acetate acts as a prodrug, which very slowly releases minute amounts of active vitamin E.

Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied.
The skin of the skh-1 mouse after ultraviolet B (280-320 nm, UVB) irradiation shows the pathological changes typical of sunburn damage: spongiosis (edematous spaces) around some cells, necrosis of keratinocytes, giving rise to sunburn cells, inflammatory infiltration of polymorphonuclear leucocytes, etc. In our previous study, these were accompanied by erythema, increased skin sensitivity, andedematous swelling. The topical application of tocopherol acetate (TA) immediately after the UVB exposure decreased these changes. In this paper, multiple measurements of the skin thickness were made at different locations along the magnetic resonance imaging (MRI) cross-sectional image of the skin. This permits effects to be quantified with (if desired) the contralateral half of the back serving as an internal control, either exposed (positive control) or unexposed (negative control). Topical application of TA resulted in an increase in the concentration of free tocopherol in the skin. No qualitative differences in ultrastructural appearance of the UVB-irradiated, TA-treated skin could be discerned by careful examination. In vivo high resolution video microscopy of blood flow in venules of the irradiated mouse ear revealed a large (tenfold) but not statistically significant decrease in stationary lymphocytes adhering to the venule walls. The delaying of the application of TA up to 8 hours after the termination of UVB irradiation still offered statistically significant protection as did immediate application of 5% TA in diluent Myritol 318 (Delios S, Henkel).Source:
Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied.Trevithick JR, Shum DT, Redae S, Mitton KP, Norley C, Karlik SJ, Groom AC, Schmidt EE. Department of Biochemistry, Faculty of Medicine, University of Western Ontario, London, Canada. Scanning Microscopy [1993, 7(4):1269-1281]http://europepmc.org/abstract/med/8023094

Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.
Abstract:
Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115–0.23 J/cm2 results after 24–48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-α-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40–55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel noninvasive technique not previously reported for this purpose—magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p < 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p < 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p < 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible 0even after the irradiation has stopped, by a derivative of d-α-tocopherol which is stable to autooxidation.Source:
Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. John R. Trevithick, Hua Xiong, Shirley Lee, David T. Shum, S.Ernest Sanford, Stephen J. Karlik , Christopher Norley, Geoffrey R. Dilworth. Archives of Biochemistry and Biophysics. Volume 296, Issue 2, 1 August 1992, Pages 575-582. doi:10.1016/0003-9861(92)90613-2

Retinyl Palmitate (Vitamin A)

Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin
Abstract
To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6–24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.

Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice
Abstract
Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4–6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for the ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.
Sources:
Z. Malik, G. Kostenich, L. Roitman, B. Ehrenberg, A. OrensteinJournal of Photochemistry and Photobiology B: BiologyVolume 28, Issue 3, June 1995, Pages 213–218. doi:10.1016/1011-1344(95)07117-Khttp://www.sciencedirect.com/science/article/pii/101113449507117K

Lexaminopeptide complex

Synthesis and Biological Evaluation in Vitro of Selective, High Affinity Peptide Antagonists of Human Melanin-Concentrating Hormone Action at Human Melanin-Concentrating Hormone Receptor 1
Abstract
Human melanin-concentrating hormone (hMCH) and many of its analogues are potent but nonspecific ligands for human melanin-concentrating hormone receptors 1 and 2 (hMCH-1R and hMCH-2R). To differentiate between the physiological functions of these receptors, selective antagonists are needed. In this study, analogues of Ac-Arg6-cyclo(S−S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13-Arg14-Pro15-Cys16)-NH2, a high affinity but nonselective agonist at hMCH-1R and hMCH-2R, were prepared and tested in binding and functional assays on cells expressing these receptors. In the new analogues, 5-aminovaleric acid (Ava) was incorporated in place of the Leu9-Gly10 and/or Arg14-Pro15 segments of the disulfide ring. Several of these compounds turned out to be high affinity antagonists selective for hMCH-1R. Moreover, even at micromolar concentrations, they were devoid of agonist potency at both hMCH receptors and not effective as hMCH-2R antagonists. For example, peptide 14, Gva6- cyclo(S−S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13-Ava14,15−Cys16)-NH2, (Gva = 5-guanidinovaleric acid), was a full competitive hMCH-1R antagonist (IC50 = 14 nM, KB = 0.9 nM) with more than 1000-fold selectivity over hMCH-2R. Examination of various compounds with Ava in positions 9,10 and/or 14,15 revealed that the Leu9-Gly10 and Arg14-Pro15 segments of the disulfide ring are the principal structural elements determining hMCH-1R selectivity and ability to act as a hMCH-1R antagonist.Source:
Maria A. Bednarek , Donna L. Hreniuk , Carina Tan , Oksana C. Palyha , Douglas J. MacNeil , Lex H. Y. Van der Ploeg , Andrew D. Howard , and Scott D. Feighner. Journal of Medicinal Chemistry , Biochemistry, 2002, 41 (20), pp 6383–6390. DOI: 10.1021/bi0200514http://pubs.acs.org/doi/abs/10.1021/bi0200514

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